Acenocoumarol: A coumarin that is used as an anticoagulant. Its actions and uses are similar to those of WARFARIN. (From Martindale, The Extra Pharmacopoeia, 30th ed, p233)Phenprocoumon: Coumarin derivative that acts as a long acting oral anticoagulant.Vitamin K Epoxide Reductases: OXIDOREDUCTASES which mediate vitamin K metabolism by converting inactive vitamin K 2,3-epoxide to active vitamin K.Anticoagulants: Agents that prevent clotting.International Normalized Ratio: System established by the World Health Organization and the International Committee on Thrombosis and Hemostasis for monitoring and reporting blood coagulation tests. Under this system, results are standardized using the International Sensitivity Index for the particular test reagent/instrument combination used.Drug Dosage Calculations: Math calculations done for preparing appropriate doses of medicines, taking into account conversions of WEIGHTS AND MEASURES. Mistakes are one of the sources of MEDICATION ERRORS.Steroid 16-alpha-Hydroxylase: A liver microsomal cytochrome P450 enzyme that catalyzes the 16-alpha-hydroxylation of a broad spectrum of steroids, fatty acids, and xenobiotics in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme is encoded by a number of genes from several CYP2 subfamilies.Pharmacogenetics: A branch of genetics which deals with the genetic variability in individual responses to drugs and drug metabolism (BIOTRANSFORMATION).Aryl Hydrocarbon Hydroxylases: A large group of cytochrome P-450 (heme-thiolate) monooxygenases that complex with NAD(P)H-FLAVIN OXIDOREDUCTASE in numerous mixed-function oxidations of aromatic compounds. They catalyze hydroxylation of a broad spectrum of substrates and are important in the metabolism of steroids, drugs, and toxins such as PHENOBARBITAL, carcinogens, and insecticides.Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.Prothrombin Time: Clotting time of PLASMA recalcified in the presence of excess TISSUE THROMBOPLASTIN. Factors measured are FIBRINOGEN; PROTHROMBIN; FACTOR V; FACTOR VII; and FACTOR X. It is used for monitoring anticoagulant therapy with COUMARINS.ButanonesHemorrhage: Bleeding or escape of blood from a vessel.Coumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.Chronic Pain: Aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain.Acute Pain: Intensely discomforting, distressful, or agonizing sensation associated with trauma or disease, with well-defined location, character, and timing.Pain: An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.Pain Management: A form of therapy that employs a coordinated and interdisciplinary approach for easing the suffering and improving the quality of life of those experiencing pain.Pain Measurement: Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.Tandem Mass Spectrometry: A mass spectrometry technique using two (MS/MS) or more mass analyzers. With two in tandem, the precursor ions are mass-selected by a first mass analyzer, and focused into a collision region where they are then fragmented into product ions which are then characterized by a second mass analyzer. A variety of techniques are used to separate the compounds, ionize them, and introduce them to the first mass analyzer. For example, for in GC-MS/MS, GAS CHROMATOGRAPHY-MASS SPECTROMETRY is involved in separating relatively small compounds by GAS CHROMATOGRAPHY prior to injecting them into an ionization chamber for the mass selection.Chromatography, Liquid: Chromatographic techniques in which the mobile phase is a liquid.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Solid Phase Extraction: An extraction method that separates analytes using a solid phase and a liquid phase. It is used for preparative sample cleanup before analysis by CHROMATOGRAPHY and other analytical methods.Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.Spectrometry, Mass, Electrospray Ionization: A mass spectrometry technique used for analysis of nonvolatile compounds such as proteins and macromolecules. The technique involves preparing electrically charged droplets from analyte molecules dissolved in solvent. The electrically charged droplets enter a vacuum chamber where the solvent is evaporated. Evaporation of solvent reduces the droplet size, thereby increasing the coulombic repulsion within the droplet. As the charged droplets get smaller, the excess charge within them causes them to disintegrate and release analyte molecules. The volatilized analyte molecules are then analyzed by mass spectrometry.Calibration: Determination, by measurement or comparison with a standard, of the correct value of each scale reading on a meter or other measuring instrument; or determination of the settings of a control device that correspond to particular values of voltage, current, frequency or other output.Thrombelastography: Use of a thrombelastograph, which provides a continuous graphic record of the physical shape of a clot during fibrin formation and subsequent lysis.Heart Valves: Flaps of tissue that prevent regurgitation of BLOOD from the HEART VENTRICLES to the HEART ATRIA or from the PULMONARY ARTERIES or AORTA to the ventricles.Blood Coagulation: The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot.Hydroxylation: Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Cytochrome P-450 Enzyme System: A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Mixed Function Oxygenases: Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia.Umbelliferones: 7-Hydroxycoumarins. Substances present in many plants, especially umbelliferae. Umbelliferones are used in sunscreen preparations and may be mutagenic. Their derivatives are used in liver therapy, as reagents, plant growth factors, sunscreens, insecticides, parasiticides, choleretics, spasmolytics, etc.4-Hydroxycoumarins: Substances found in many plants, containing the 4-hydroxycoumarin radical. They interfere with vitamin K and the blood clotting mechanism, are tightly protein-bound, inhibit mitochondrial and microsomal enzymes, and are used as oral anticoagulants.2-Hydroxy-5-nitrobenzyl Bromide: A chemical reagent that reacts with and modifies chemically the tryptophan portion of protein molecules. Used for 'active site' enzyme studies and other protein studies. Sometimes referred to as Koshland's reagent.Factor VII: Heat- and storage-stable plasma protein that is activated by tissue thromboplastin to form factor VIIa in the extrinsic pathway of blood coagulation. The activated form then catalyzes the activation of factor X to factor Xa.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Commerce: The interchange of goods or commodities, especially on a large scale, between different countries or between populations within the same country. It includes trade (the buying, selling, or exchanging of commodities, whether wholesale or retail) and business (the purchase and sale of goods to make a profit). (From Random House Unabridged Dictionary, 2d ed, p411, p2005 & p283)Therapeutic Equivalency: The relative equivalency in the efficacy of different modes of treatment of a disease, most often used to compare the efficacy of different pharmaceuticals to treat a given disease.Tablets: Solid dosage forms, of varying weight, size, and shape, which may be molded or compressed, and which contain a medicinal substance in pure or diluted form. (Dorland, 28th ed)Drugs, Generic: Drugs whose drug name is not protected by a trademark. They may be manufactured by several companies.Terminology as Topic: The terms, expressions, designations, or symbols used in a particular science, discipline, or specialized subject area.Drug Prescriptions: Directions written for the obtaining and use of DRUGS.Capsules: Hard or soft soluble containers used for the oral administration of medicine.Tablets, Enteric-Coated: Tablets coated with material that delays release of the medication until after they leave the stomach. (Dorland, 28th ed)Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population.ThiazinesSweetening Agents: Substances that sweeten food, beverages, medications, etc., such as sugar, saccharine or other low-calorie synthetic products. (From Random House Unabridged Dictionary, 2d ed)TriazolesAlloxanCarcinogenicity Tests: Tests to experimentally measure the tumor-producing/cancer cell-producing potency of an agent by administering the agent (e.g., benzanthracenes) and observing the quantity of tumors or the cell transformation developed over a given period of time. The carcinogenicity value is usually measured as milligrams of agent administered per tumor developed. Though this test differs from the DNA-repair and bacterial microsome MUTAGENICITY TESTS, researchers often attempt to correlate the finding of carcinogenicity values and mutagenicity values.Albendazole: A benzimidazole broad-spectrum anthelmintic structurally related to MEBENDAZOLE that is effective against many diseases. (From Martindale, The Extra Pharmacopoeia, 30th ed, p38)
A placebo-controlled study of interaction between nabumetone and acenocoumarol. (1/76)
AIMS: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients treated with oral anticoagulants is generally discouraged due to the risk of interactions that could increase the risk of bleeding complications. Available data suggest the NSAID, nabumetone, does not produce such an interaction. We investigated whether nabumetone would interact with acenocoumarol, an oral anticoagulant widely used in some European countries. METHODS: A double-blind, randomized, placebo-controlled study was conducted evaluating nabumetone (1-2 g daily for up to 4 weeks) in osteoarthritis patients with thromboembolic risk previously stabilized on acenocoumarol. The primary efficacy end point was the proportion of patients whose International Normalized Ratio (INR) remained within established margins and whose acenocoumarol dose was not changed. Fifty-six patients were randomized to receive nabumetone (n=27) or placebo (n=29). RESULTS: Eighteen patients in each group (67% for nabumetone and 62% for placebo) completed the study without showing INR or acenocoumarol dose changes, and were considered as study successes. Nine patients (33%) with nabumetone and 11 (38%) with placebo were considered study failures in the intention-to-treat analysis (one patient on nabumetone and four on placebo did not complete the study due to reasons not related to INR and acenocoumarol dose changes). No significant differences were found between groups with regard to study successes. There were two minor bleeding complications, one in each group. Six patients per group presented with eight adverse experiences in each group. CONCLUSIONS: Treatment with nabumetone did not alter INR levels compared with placebo in patients stabilized on oral acenocoumarol who require NSAID therapy. These results suggest that nabumetone does not produce a clinically relevant interaction with acenocoumarol. In orally anticoagulated patients without other associated risk factors, treatment with nabumetone for up to 4 weeks does not require increased monitoring of INR levels. (+info)Prediction of pharmacokinetic drug/drug interactions from In vitro data: interactions of the nonsteroidal anti-inflammatory drug lornoxicam with oral anticoagulants. (2/76)
CYP2C9 is involved in the metabolism of the oral anticoagulants warfarin, phenprocoumon, and acenocoumarol. It is also responsible for the 5'-hydroxylation of the nonsteroidal anti-inflammatory drug lornoxicam. Therefore, lornoxicam and the oral anticoagulants are potential inhibitors of their metabolism. Their inhibitory potency was investigated in microsomes from six human livers. An approach to predict pharmacokinetic interactions of lornoxicam from in vitro inhibition data was developed. Where possible, the forecasts were verified by comparison with data from clinical interaction studies. The following increases in steady-state plasma concentrations or areas under the plasma concentration-time curve of the oral anticoagulants by concomitant lornoxicam medication were predicted (values in parentheses are for healthy volunteers): (S)-warfarin, 1. 58-fold (1.32-fold for racemate); racemic-acenocoumarol, 1.28-fold (1.09-fold); (R)-acenocoumarol, 1.10-fold (1.0-fold); racemic-phenprocoumon, 1.11-fold (1.18-fold); and (S)-phenprocoumon, 1.13-fold (1.24-fold). Lornoxicam 5'-hydroxylation was competitively inhibited in vitro by both phenprocoumon (K(i) = 1.2 +/- 0.4 microM) and acenocoumarol (K(i) = 5.5 +/- 3.5 microM). The present results indicate that relatively close predictions of the interactions of lornoxicam with oral anticoagulants from in vitro data are possible under the assumption that hepatic lornoxicam concentrations are similar to its total plasma concentrations. The degree of pharmacokinetic interactions exhibited by oral anticoagulants and lornoxicam is dependent on the respective contribution of CYP2C9 to their total clearance. (+info)Assessment of patient capability to self-adjust oral anticoagulant dose: a multicenter study on home use of portable prothrombin time monitor (COAGUCHECK). (3/76)
BACKGROUND AND OBJECTIVES: Self-testing and self-monitoring with portable prothrombin time (PT) monitors has been shown to be feasible and safe. However the ability of patients on chronic oral anticoagulant therapy (OAT) to self-adjust their dose without specific training has never been properly evaluated. The aims of this study were to evaluate: 1) the ability of patients on chronic OAT to self-adjust their dose without specific training; 2) the integration of a portable PT monitor (Coagucheck, Roche Diagnostics, Germany) for home use into routine patient care in anticoagulation clinics. DESIGN AND METHODS: A nested case-control study was conducted in four centers of the Italian Federation of Anticoagulation Clinics (FCSA). Patients (n=78) on stable OAT for at least 6 months (cases: 47 men, 31 women, age range: 18-75 years) were enrolled on a volunteer basis after passing an Abbreviated Mental Test and providing informed consent. After three instruction sessions on the use of Coaguchek, subjects performed the PT test at home, communicated the INR results to the Center and suggested the dose adjustment and date for next control as they thought appropriate. However, they were requested to follow the prescription made by the Center. Controls (78 subjects) matched by age (+/- 5 years), sex and therapeutic range with the cases, were selected from among those who attended the anticoagulation clinics and managed by usual care. RESULTS: When compared with the dose prescribed by the Clinic, the dose suggested by warfarin and acenocoumarol users was equal to or within +/- 6% of the mean weekly dose in 80% and 82% of suggestions, respectively. Time spent in the therapeutic range during the study was the same (80%) for cases and controls. INTERPRETATION AND CONCLUSIONS: Selected patients on chronic anticoagulant therapy can acquire a satisfactory ability for self-adjustment of OAT dose without specific training. (+info)Cytochrome P4502C9 is the principal catalyst of racemic acenocoumarol hydroxylation reactions in human liver microsomes. (4/76)
The oral anticoagulant acenocoumarol is given as a racemic mixture. The (S)-enantiomer is rapidly cleared and is the reason why only (R)-acenocoumarol contributes to the pharmacological effect. The objective of the study was to establish the cytochrome P450 (CYP) enzymes catalyzing the hydroxylations of the acenocoumarol enantiomers. Of various cDNA-expressed human CYPs, only CYP2C9 hydroxylated (S)-acenocoumarol. Hydroxylation occurred at the 6-, 7-, and 8-position with equal K(m) values and a ratio of 0.9:1:0.1 for V(max). CYP2C9 also mediated the 6-, 7-, and 8-hydroxylations of (R)-acenocoumarol with K(m) values three to four times and V(max) values one-sixth times those of (S)-acenocoumarol. (R)-Acenocoumarol was also metabolized by CYP1A2 (6-hydroxylation) and CYP2C19 (6-, 7-, and 8-hydroxylation). In human liver microsomes one enzyme only catalyzed (S)-acenocoumarol hydroxylations with K(m) values < 1 microM. In most of the samples tested the 7-hydroxylation of (R)-acenocoumarol was also catalyzed by one enzyme only. The 6-hydroxylation was catalyzed by at least two enzymes. Sulfaphenazole could completely inhibit in a competitive way the hydroxylations of (S)-acenocoumarol and the 7-hydroxylation of (R)-acenocoumarol. The 6-hydroxylation of (R)-acenocoumarol could be partially inhibited by sulfaphenazole, 40 to 50%, and by furafylline, 20 to 30%. Significant mutual correlations were obtained between the hydroxylations of (S)-acenocoumarol, the 7-hydroxylation of (R)-acenocoumarol, the 7-hydroxylation of (S)-warfarin, and the methylhydroxylation of tolbutamide. The results demonstrate that (S)-acenocoumarol is hydroxylated by a single enzyme, namely CYP2C9. CYP2C9 is also the main enzyme in the 7-hydroxylation of (R)-acenocoumarol. Other enzymes involved in (R)-acenocoumarol hydroxylation reactions are CYP1A2 and CYP2C19. Drug interactions must be expected, particularly for drugs interfering with CYP2C9. Also, drugs interfering with CYP1A2 and CYP2C19 may potentiate acenocoumarol anticoagulant therapy. (+info)Low molecular weight heparin versus oral anticoagulants in the long-term treatment of deep venous thrombosis. (5/76)
PURPOSE: The purpose of this study was to evaluate whether low molecular weight heparin (LMWH) could be equal or more effective than conventional oral anticoagulants (OAs) in the long-term treatment of deep venous thrombosis (DVT). METHODS: One hundred fifty-eight patients with symptomatic DVT of the lower limbs confirmed by means of duplex ultrasound scan were randomized to receive 3 to 6 months' treatment with nadroparine calcium or acenocoumarol. Quantitative and qualitative duplex scan scoring systems were used to study the evolution of thrombosis in both groups at 1, 3, 6, and 12 months. RESULTS: During the 12-month surveillance period, two (2.5%) of the 81 patients who received LMWH and seven (9%) of the 77 patients who received OAs had recurrence of venous thrombosis (not significant). In the LMWH group no cases of major bleeding were found, and four cases (5.2%) occurred in the OA group (not significant). The mortality rate was nine (11.1%) in the LMWH group and 7.8% in the OA group (not significant). The quantitative mean duplex scan score decreased in both groups during the follow-up and had statistical significance after long-term LMWH treatment on iliofemoral DVT (1, 3, 6, and 12 months), femoropopliteal DVT (1-3 months), and infrapopliteal DVT (first month). Duplex scan evaluation showed that the rate of venous recanalization significantly increased in the common femoral vein at 6 and at 12 months and during each point of follow-up in the superficial and popliteal veins in the LMWH group. Reflux was significantly less frequent in communicating veins after LMWH treatment (17.9% vs 32.2% in the OA group). The reflux rates in the superficial (22.4% in the LMWH group, 30.6% in OA group) and deep (13.4% vs 17.7%) venous system showed no significant differences between groups. CONCLUSIONS: The unmonitored subcutaneous administration of nadroparine in fixed daily doses was more effective than oral acenocoumarol with laboratory control adjustment in achieving recanalization of leg thrombi. With nadroparine, there was less late valvular communicating vein insufficiency, and it was at least as efficacious and safe as oral anticoagulants after long-term administration. These results suggest that LMWHs may therefore represent a real therapeutic advance in the long-term management of DVT. (+info)Optimal oral anticoagulant intensity to prevent secondary ischemic and hemorrhagic events in patients after infrainguinal bypass graft surgery. Dutch BOA Study Group. (6/76)
OBJECTIVES: The purpose of this study was to determine the optimal intensity of oral anticoagulation in patients who participated in a randomized trial of oral anticoagulants or aspirin after infrainguinal bypass graft surgery. METHODS: The distribution of patient-time spent in international normalized ratio (INR) classes of 0.5 INR unit was calculated assuming a linear change between successive measurements. INR-specific incidence rates of ischemic and hemorrhagic events were calculated as the ratio of the number of events at a certain INR category and the total patient-time spent in that class. The relationship between INR class and event rates was quantified by rate ratios calculated in a Poisson regression model. RESULTS: In 1326 patients (mean age, 69 years) 41,928 INR measurements were recorded in 1698 patient-years. Patients spent 50% of the total time within the target range of 3.0 to 4.5 INR. Most of the patient-time (60%) was spent between 2.5 and 3.5 INR. For each increasing class of 0.5 INR, the incidence of ischemic events (n = 154, INR data on event available in 49%) decreased by a factor of 0.97 (95% CI, 0.87-1.08). The incidence of major bleeding (n = 123, INR data on event available in 65%) increased significantly by a factor of 1.27 (95% CI, 1.19-1.34) for each increasing 0.5 INR category. The optimal target range was 3.0 to 4.0 INR, with an incidence of 3.8 events (0.9 ischemic and 2.9 hemorrhagic) per 100 patient-years. CONCLUSIONS: The target range of 3.0 to 4.0 INR is the optimal range of achieved anticoagulation intensity and is safe for the prevention of ischemic events in patients after infrainguinal bypass graft surgery. (+info)Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. Warfarin Optimal Duration Italian Trial Investigators. (7/76)
BACKGROUND: In patients with idiopathic deep venous thrombosis, continuing anticoagulant therapy beyond three months is associated with a reduced incidence of recurrent thrombosis during the period of therapy. Whether this benefit persists after anticoagulant therapy is discontinued is controversial. METHODS: Patients with a first episode of idiopathic proximal deep venous thrombosis who had completed three months of oral anticoagulant therapy (with warfarin, in 97 percent of the cases and acenocoumarol in 3 percent) were randomly assigned to the discontinuation of oral anticoagulants or to their continuation for nine additional months. The primary study outcome was recurrence of symptomatic, objectively confirmed venous thromboembolism during at least two years of follow-up. RESULTS: The primary intention-to-treat analysis showed that of 134 patients assigned to continued oral anticoagulant therapy, 21 had a recurrence of venous thromboembolism (15.7 percent; average follow-up, 37.8 months), as compared with 21 of 133 patients assigned to the discontinuation of oral anticoagulant therapy (15.8 percent; average follow-up, 37.2 months), resulting in a relative risk of 0.99 (95 percent confidence interval, 0.57 to 1.73). During the initial nine months after randomization (after all patients received three months of therapy), 1 patient had a recurrence while receiving oral anticoagulant therapy (0.7 percent), as compared with 11 of the patients assigned to the discontinuation of oral anticoagulant therapy (8.3 percent; P=0.003). The incidence of recurrence after the discontinuation of treatment was 5.1 percent per patient-year in patients in whom oral anticoagulant therapy was discontinued after 3 months (95 percent confidence interval, 3.2 to 7.5 percent; average interval since discontinuation, 37.2 months) and 5.0 percent per patient-year in patients who received an additional 9 months of oral anticoagulant therapy (95 percent confidence interval, 3.1 to 7.8 percent; average interval since discontinuation, 29.4 months). None of the recurrences were fatal. Four patients had non-fatal major bleeding during the extended period of anticoagulant therapy (3.0 percent). CONCLUSIONS: In patients with idiopathic deep venous thrombosis, the clinical benefit associated with extending the duration of anticoagulant therapy to one year is not maintained after the therapy is discontinued. (+info)Determination of coumarin-type anticoagulants in human plasma by HPLC-electrospray ionization tandem mass spectrometry with an ion trap detector. (8/76)
BACKGROUND: Coumarin-type anticoagulants are used for the long-term treatment and prevention of thromboembolic disorders. The identification of these drugs is crucial in patients with an increased prothrombin time of unknown origin. The aim of this study was to develop a sensitive and specific method for the simultaneous determination of phenprocoumon, acenocoumarol, and warfarin in human plasma by HPLC-electrospray ionization tandem mass spectrometry. METHODS: After addition of the internal standard, p-chlorowarfarin, plasma samples were extracted using Oasis MCX solid-phase extraction cartridges. The compounds were separated on a Symmetry C18 column (Waters) with a mobile phase of acetonitrile-1 g/L formic acid (75:25 by volume) at a flow rate of 0.5 mL/min. RESULTS: Extraction and separation of the three drugs and the internal standard were accomplished in 9 min. The overall extraction efficiency was >89% for all three compounds. The limits of detection were 1 microg/L for phenprocoumon and warfarin and 10 microg/L for acenocoumarol. Regression analysis of the calibration data revealed good correlation (r(2) >or=0.995) for all compounds. Within-run accuracies for quality-control samples were +/- 1% to 7% of the target concentration, with CVs <9%. CONCLUSIONS: The proposed method enables the unambiguous identification and quantification of phenprocoumon, warfarin, and acenocoumarol in both clinical and forensic specimens. This method combines a new, rapid solid-phase extraction procedure with an extremely fast chromatographic analysis, which is especially advantageous for clinical laboratories. (+info)B01AA07 Acenocoumarol. B01AA08 Ethyl biscoumacetate. B01AA09 Clorindione. B01AA10 Diphenadione. B01AA11 Tioclomarol. B01AA12 ...
... may increase the anticoagulant activities of acenocoumarol. The risk or severity of adverse effects can be ...
Other examples are acenocoumarol, phenprocoumon, atromentin, and phenindione. The coumarins brodifacoum and difenacoum are used ...
In some European countries, other coumarin derivatives (phenprocoumon and acenocoumarol) are used. These agents, so-called ...
The fluoroquinolones have been shown to increase the anticoagulant effect of Acenocoumarol, Anisindione, and Dicumarol. ...
... such as acenocoumarol and phenprocoumon. These have a shorter (acenocoumarol) or longer (phenprocoumon) half-life, and are not ...
Warfarin (Coumadin) Coumatetralyl Phenprocoumon Acenocoumarol Dicoumarol Tioclomarol Brodifacoum Another group of VKAs are 1,3- ...
A 1987 report described the use of DCP determination in the detection of intoxication with acenocoumarol, a vitamin K ...
... is pharmacologically important as a target of anticoagulant drugs warfarin and related coumarins such as acenocoumarol, ...
2008). "Improvement in the regulation of the vitamin K antagonist acenocoumarol after a standard initial dose regimen: ...
... used to make warfarin and acenocoumarol). In Ex1 of Dietifen patent, deanol ether is described. Shorthand notation is also ...
Pharmaceutical examples of 4-hydroxycoumarin pharmaceuticals include: acenocoumarol dicoumarol ethyl biscoumacetate ...
... doses guided by genotype-phenotype and in their standard management in patients who initiate anticoagulation with acenocoumarol ...
In some countries, other coumarins are used instead of warfarin, such as acenocoumarol and phenprocoumon. These have a shorter ... acenocoumarol) or longer (phenprocoumon) half-life, and are not completely interchangeable with warfarin. Several types of ...
... acenocoumarol MeSH D03.438.150.446.520.203 --- dicumarol MeSH D03.438.150.446.520.451 --- ethyl biscoumacetate MeSH D03.438. ... acenocoumarol MeSH D03.830.219.446.520.203 --- dicumarol MeSH D03.830.219.446.520.451 --- ethyl biscoumacetate MeSH D03.830. ...
Warfarin, phenprocoumon, and acenocoumarol are orally active vitamin K antagonists (VKA) which decrease hepatic synthesis of a ...
... drugs with a narrow therapeutic index such as warfarin and phenytoin and other routinely prescribed drugs such as acenocoumarol ...
Whereas, the orally active warfarin, phenprocoumon, and acenocoumarol are vitamin K antagonists (VKA) decrease a number of ...
... acenocoumarol (INN) Aceon aceperone (INN) Acephen acepromazine (INN) aceprometazine (INN) acequinoline (INN) acesulfame (INN) ...
... acenocoumarol, or phenprocoumon therapy is commenced (this may take several days, usually while the patient is in the hospital ...
... is an anticoagulant that functions as a vitamin K antagonist (like warfarin). It is a derivative of coumarin and ... Drugs.com Drugs.com international listings for acenocoumarol DDB 29202 Cesar J, GarcĂa-Avello A, Navarro J, Herraez M (2004). " ... Lengyel M; SPORTIF-III Altanulmány VizsgálĂłi (2004). "Warfarin or acenocoumarol is better in the anticoagulant treatment of ... Ufer M (2005). "Comparative pharmacokinetics of vitamin Kd antagonists: warfarin, phenprocoumon and acenocoumarol". Clin ...
When plasmin breaks down fibrin, a number of soluble parts are produced. These are called fibrin degradation products (FDPs). FDPs compete with thrombin, and thus slow down clot formation by preventing the conversion of fibrinogen to fibrin. This effect can be seen in the thrombin clotting time (TCT) test, which is prolonged in a person that has active fibrinolysis.. FDPs, and a specific FDP, the D-dimer, can be measured using antibody-antigen technology. This is more specific than the TCT, and confirms that fibrinolysis has occurred. It is therefore used to indicate deep-vein thrombosis, pulmonary embolism, DIC and efficacy of treatment in acute myocardial infarction. Alternatively, a more rapid detection of fibrinolytic activity, especially hyperfibrinolysis, is possible with thromboelastometry (TEM) in whole blood, even in patients on heparin. In this assay, increased fibrinolysis is assessed by comparing the TEM profile in the absence or presence of the fibrinolysis inhibitor aprotinin. ...
In 2001, Eli Lilly's chairman, president and CEO, Sidney Taurel, told shareholders: "No medicine better symbolizes our mission than Xigris," calling it "one of our industry's genuine breakthroughs."[5]. Xigris was designed to fight sepsis, a condition that kills more than 200,000 Americans annually. It was the only approved drug for sepsis, and it costs $8,000 to treat a single patient. Lilly hoped it would be a blockbuster, with sales of at least a billion dollars a year. But after five years on the market, sales were only $200 million.. Eli Lilly used the Belsito & Company PR firm in a marketing campaign to promote Xigris, its drug for treatment of sepsis. A report in the New England Journal of Medicine (NEJM) accused the company of initiating false reports of a shortage of the drug to boost sales.[6] Belsito and Company spread the word that the drug was being "rationed" and physicians were being 'systematically forced' to decide who would live and who would die. As part of this effort, Lilly ...
Acetylsalicylic acid is a weak acid, and very little of it is ionized in the stomach after oral administration. Acetylsalicylic acid is quickly absorbed through the cell membrane in the acidic conditions of the stomach. The increased pH and larger surface area of the small intestine causes aspirin to be absorbed more slowly there, as more of it is ionised. Owing to the formation of concretions, aspirin is absorbed much more slowly during overdose, and plasma concentrations can continue to rise for up to 24 hours after ingestion.[152][153][154] About 50-80% of salicylate in the blood is bound to albumin protein, while the rest remains in the active, ionized state; protein binding is concentration-dependent. Saturation of binding sites leads to more free salicylate and increased toxicity. The volume of distribution is 0.1-0.2 L/kg. Acidosis increases the volume of distribution because of enhancement of tissue penetration of salicylates.[154] As much as 80% of therapeutic doses of salicylic acid is ...
The drug is clear with a pH of 10.[7] Its production is inhibited indirectly by NSAIDs, which inhibit the cyclooxygenase enzymes COX1 and COX2. These convert arachidonic acid to prostaglandin H2 (PGH2), the immediate precursor of prostacyclin. Since thromboxane (an eicosanoid stimulator of platelet aggregation) is also downstream of COX enzymes, one might think that the effect of NSAIDs would act to balance. However, prostacyclin concentrations recover much faster than thromboxane levels, so aspirin administration initially has little to no effect but eventually prevents platelet aggregation (the effect of prostaglandins predominates as they are regenerated). This is explained by understanding the cells that produce each molecule, TXA2 and PGI2. Since PGI2 is primarily produced in a nucleated endothelial cell, the COX inhibition by NSAID can be overcome with time by increased COX gene activation and subsequent production of more COX enzymes to catalyze the formation of PGI2. In contrast, TXA2 is ...
Acenocoumarol Aged Anticoagulants Drug Administration Schedule Drug Monitoring Drug Tolerance Elective Surgical Procedures ... Patients on oral anticoagulation with acenocoumarol after elective heart valve replacement were prospectively included in the ... Reliability of thromboelastometry for detecting the safe coagulation threshold in patients taking acenocoumarol after elective ... Reliability of thromboelastometry for detecting the safe coagulation threshold in patients taking acenocoumarol after elective ...
CYP2C9 is also the main enzyme in the 7-hydroxylation of (R)-acenocoumarol. Other enzymes involved in (R)-acenocoumarol ... acenocoumarol hydroxylations with Km values , 1 mM. In most of the samples tested the 7-hydroxylation of (R)-acenocoumarol was ... acenocoumarol. The 6-hydroxylation of (R)acenocoumarol could be partially inhibited by sulfaphenazole, 40 to 50%, and by ... acenocoumarol. (R)Acenocoumarol was also metabolized by CYP1A2 (6-hydroxylation) and CYP2C19 (6-, 7-, and 8-hydroxylation). In ...
Pharmacogenetics of acenocoumarol pharmacodynamics.. In: Clinical pharmacology and therapeutics, Vol. 75, no. 5, p. 403-14 ( ... Acenocoumarol - administration & dosage - pharmacokinetics - pharmacology ; Administration, Oral ; Adolescent ; Adult ; Aged ; ... Finally, CYP2C9 phenotype was evaluated after a single oral dose of 4 mg of acenocoumarol. Factor VII coagulant activity was ... The haplotype that contains the CYP2C9*3 allele was the only one influencing acenocoumarol pharmacodynamics, explaining 14.3% ...
Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity.. ... Acenocoumarol - administration & dosage ; Administration, Oral ; Adolescent ; Adult ; Aged ; Anticoagulants - administration & ... Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity. ... Home» Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol ...
Acenocoumarol is an anticoagulant that functions as a vitamin K antagonist (like warfarin). It is a derivative of coumarin and ... Drugs.com Drugs.com international listings for acenocoumarol DDB 29202 Cesar J, GarcĂa-Avello A, Navarro J, Herraez M (2004). " ... Lengyel M; SPORTIF-III Altanulmány VizsgálĂłi (2004). "Warfarin or acenocoumarol is better in the anticoagulant treatment of ... Ufer M (2005). "Comparative pharmacokinetics of vitamin Kd antagonists: warfarin, phenprocoumon and acenocoumarol". Clin ...
If you have an allergy to acenocoumarol or any other part of this drug. ...
Si es alérgico al acenocoumarol o cualquier otro componente de este medicamento. ...
Genetic determinants of acenocoumarol and phenprocoumon maintenance dose requirements.. Cadamuro J1, Dieplinger B, Felder T, ... Acenocoumarol (AC) and phenprocoumon (PC) are coumarin derivates widely prescribed in European countries for the prevention and ...
Stable treatment with acenocoumarol Patients in stable anticoagulant treatment with acenocoumarol for auricular fibrillation, ... Pharmacogenetic Dosage Algorithm for Acenocoumarol. The safety and scientific validity of this study is the responsibility of ... Genetic: Acenocoumarol A blood sample was collected for CYP2C9, VKORC1, CYP4F2, APOE and 2 variants of POR genotypes. ... Creation of a pharmacogenetic algorithm of dosage for acenocoumarol [ Time Frame: Up to 5 years ]. ...
Validation of the acenocoumarol EU-PACT algorithms: similar performance in the Rotterdam Study cohort as in the original study ... A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon. N Engl J Med. 2013 Dec 12;369(24):2304-12. doi ... Long-term anticoagulant effects of the CYP2C9 and VKORC1 genotypes in acenocoumarol users. J Thromb Haemost. 2012 Apr;10(4):606 ... Evaluation of the effect of statin use on the acenocoumarol and phenprocoumon maintenance dose. Drug Metabol Drug Interact. ...
Leflunomide may increase the anticoagulant effect of acenocoumarol.. Trimetrexate. The anticoagulant effect of Acenocoumarol, a ... The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Acenocoumarol by decreasing Acenocoumarol ... The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Acenocoumarol by decreasing Acenocoumarol ... Thiopental may increase the metabolism of the Vitamin K antagonist, Acenocoumarol. Acenocoumarol dose adjustment may be ...
... acenocoumarol and phenprocoumo were found in PRIME PubMed. Download Prime PubMed App to iPhone, iPad, or Android ... AcenocoumarolAlgorithmsAnticoagulantsClinical Trials as TopicCost-Benefit AnalysisCytochrome P-450 CYP2C9Drug Dosage ... Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon. Br J Clin ... Pharmacogenetic-guided Dosing of Coumarin Anticoagulants: Algorithms for Warfarin, Acenocoumarol and Phenprocoumon. Br J Clin ...
... acenocoumarol explanation free. What is acenocoumarol? Meaning of acenocoumarol medical term. What does acenocoumarol mean? ... Looking for online definition of acenocoumarol in the Medical Dictionary? ... acenocoumarol. Also found in: Encyclopedia, Wikipedia. Acenocoumarol. A fast-acting vitamin K-antagonist anticoagulant. In ... acenocoumarol. A fast-acting vitamin K-antagonist anticoagulant. acenocoumarol, acenocoumarin. a warfarin derivative used as an ...
The mean absolute error of the predicted acenocoumarol dose (mg/week) obtained with the pharmacogenetic algorithm was 3.63 vs. ... We ascertained the influence of clinical and genetic variables on the stable acenocoumarol dose by multiple linear regression ... and some pharmacogenetic-guided dosing algorithms for warfarin and acenocoumarol have been developed for mixed populations. We ...
There are none...: Even the strongest opiates only "take the edge off" for people in chronic pain. Meds are only one part of dealing with the pain. A useful tool, but pain is so necessary for survival that we are not "allowed" to monkey with it much. In acute pain, the transition from miserable to less miserable can be great. In chronic pain, its just part of the plan. ...Read more ...
... method for the determination of R-acenocoumarol and S-acenocoumarol in human plasma was developed and validated at IPRC ... The method was validated over a linear range of 0.40 - 40.00 ng/ml for R-acenocoumarol and 0.20 - 20.00 ng/ml for the S- ... The method was successfully applied for the determination of R and S-acenocoumarol in plasma samples of 28 healthy subjects who ... acenocoumarol. Method validation covered different parameters such as linearity, accuracy, precision and stability. ...
Acenocoumarol is effective and safe in all age groups. It offers an advantage over warfarin in terms of better stability of ... Acenocoumarol is mono-coumarin derivative with racemic mixture of R (+) and S (-) enantiomers. Efficacy and safety of ... Due to its economic advantage acenocoumarol may be suitable oral anticoagulant for long term use in countries like India. ... acenocoumarol has been evaluated in atrial fibrillation, cardiac valve replacement, after myocardial infarction, treatment of ...
acenocoumarol after adjustment for the CHA2DS2-VASc score [hazard ratio (HR)dabigatran = 0.72, 95% CI: 0.20-2.63, P = 0.61]. ... 3.7%/year acenocoumarol-treated patients. The actual incidence rate of stroke or systemic embolism was 0.8%/year [95% ... acenocoumarol (vitamin K antagonist) in patients with atrial fibrillation (AF) in daily clinical practice. ... 4.3%/year (95% CI: 2.9-6.2) in acenocoumarol. This over 50% reduction remained significant after adjustment for the HAS-BLED ...
acenocoumarol ligand page. Quantitative data and detailed annnotation of the targets of licensed and experimental drugs. ... Acenocoumarol is a coumarin that is used as an anticoagulant, with actions and uses similar to warfarin. The coumarins are ...
Chemically, acenocoumarol is 3-(alpha-acetonyl-4-nitrobenzyl)-4-hydroxycoumarin.. Indications. Acenocoumarol is indicated in ... Acenocoumarol is an oral anticoagulant of the coumarin series, synthesized and developed in the Geigy laboratoires in the late ...
Acenocoumarol inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K ... Acenocoumarol inhibits the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of certain glutamic acid ... Both the extrinsic (via factors VII, X and II) and intrinsic (via factors IX, X and II) are affected by acenocoumarol. ... LGM Pharma is a Acenocoumarol CAS# 152-72-7 API supplier distributor based in the USA. Inquire about DMF, cGMP, price, ...
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Details About Generic Salt :: Acenocoumarol Main Medicine Class:: Hematological System Sub Medicine Class :: Anti Coagulants. ... 1 Details About Generic Salt :: Acenocoumarol *2 Main Medicine Class:: Hematological System Sub Medicine Class :: Anti ...
... trader of Acenocoumarol (Nicoumalone), C19H15NO6 at the best price. ... Uses: Acenocoumarol (also called nicoumalone) is used to prevent and treat harmful blood clots, reducing the risk of a stroke ... Furthermore, our esteemed customers can get Acenocoumarol (Nicoumalone) at pocket friendly prices. ... supplying quality assured Acenocoumarol (Nicoumalone). Offered pharmaceutical ingredients are used in the treatment of blood ...
Drug Search > Acenocoumarol Prescription Drug Search. Strengths available for Acenocoumarol :. Acenocoumarol 1mg. Acenocoumarol ... PharmaWiki - Acenocoumarol. Acenocoumarol Arzneimittelgruppen Antithrombotika Vitamin-K-Antagonisten Acenocoumarol ist ein ... Acenocoumarol - Wikipedia. Acenocoumarol is een coumarinederivaat dat gebruikt wordt als anticoagulans, dus om de bloedstolling ... ANTICOAGULANTS (Systemic) - Acenocoumarol Advanced Patient .... Detailed drug Information for Acenocoumarol. Includes common ...
- Human liver microsomal metabolism of the enantiomers of warfarin and acenocoumarol: P450 isozyme diversity determines the differences in their pharmacokinetics. (semanticscholar.org)
- T and the CYP2C9*3 polymorphisms, could thus predict a high risk of overdose before initiation of anticoagulation with acenocoumarol, and provide a safer and more individualized anticoagulant therapy. (uclouvain.be)
- Pharmacogenetics of acenocoumarol pharmacodynamics. (uclouvain.be)
- The haplotype that contains the CYP2C9*3 allele was the only one influencing acenocoumarol pharmacodynamics, explaining 14.3% of its interindividual variability. (uclouvain.be)
- Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity. (uclouvain.be)
- Of various cDNA-expressed human CYPs, only CYP2C9 hydroxylated (S)-acenocoumarol. (semanticscholar.org)
- Impact of CYP2C9 polymorphisms on the vulnerability to pharmacokinetic drug-drug interactions during acenocoumarol treatment. (semanticscholar.org)
- Finally, CYP2C9 phenotype was evaluated after a single oral dose of 4 mg of acenocoumarol. (uclouvain.be)
- CONCLUSION: Overall, CYP2C9-related genetic variability accounts for 14% of the interindividual variability in acenocoumarol pharmacodynamic response. (uclouvain.be)
- The oral anticoagulant acenocoumarol is given as a racemic mixture. (semanticscholar.org)
- The objective of the study was to establish the cytochrome P450 (CYP) enzymes catalyzing the hydroxylations of the acenocoumarol enantiomers. (semanticscholar.org)
- (uclouvain.be)
- Body weight explained 5% of acenocoumarol pharmacodynamic variability, whereas the NQO1*2 allele had no significant effect. (uclouvain.be)
- The aim of the study is to explore the contribution of genetic factors related either to drug metabolism (cytochrome P450 2C9) or to drug target (vitamin K epoxide reductase) to variability in the response to acenocoumarol among 222 healthy volunteers after a single oral dose. (uclouvain.be)
- Factor VII coagulant activity was measured before and 24 hours after acenocoumarol intake. (uclouvain.be)