• The effects of hepatic uptake and efflux transporters on metabolism of digoxin were examined in isolated rat hepatocytes versus microsomes. (aspetjournals.org)
  • These results strongly suggest that the hepatic uptake and efflux transporters that are found in hepatocytes, but not in microsomes, modulate intracellular concentration of digoxin and thus affect metabolism. (aspetjournals.org)
  • In the second study, rats were infused with [3- 3 H]glucose to assess whole body glucose metabolism and the ability of EtOH to alter the glucose metabolic response to epinephrine. (psu.edu)
  • This information then can be used to optimize the structure of a lead compound or chemical series to slow the rate of metabolism and therefore reduce hepatic clearance. (chromatographyonline.com)
  • Since the metabolism of galactose is dependent on liver blood flow and hepatic functional mass, further studies are needed. (hindawi.com)
  • Galactose is a C-4 epimer of glucose and is catalyzed to glucose-1-phosphate by galactokinase, the rate-limiting step of metabolism for galactose exclusively in the liver [ 5 , 6 ]. (hindawi.com)
  • No DPP-4 inhibitor has been shown to inhibit or to induce hepatic CYP-mediated drug metabolism. (nih.gov)
  • Interest continues to grow in the use of metabolic systems, in vitro , for predicting metabolism and drug interactions, in vivo . (aspetjournals.org)
  • These data indicate that the miR-34a-HNF4α pathway is activated under common conditions of metabolic stress and may have a role in the pathogenesis of NAFLD and in regulating plasma lipoprotein metabolism. (nihatodabasi.com)
  • Lipoprotein metabolism is con-trolled by the activity of functional proteins (enzymes, cell surface receptors, receptor ligands) that deter-mine the rate at which lipoproteins enter and leave the system, and by the physicochemical properties of the lipoprotein themselves. (nihatodabasi.com)
  • Our study identifies ILRUN as a completely novel regulator of lipid and lipoprotein metabolism that promotes hepatic lipoprotein … Two plasmalipoproteins, LDL and HDL, and one plasma lipid, triglyceride (TG), play an important role in this pathway. (nihatodabasi.com)
  • Hepatic Cholesterol Metabolism. (nihatodabasi.com)
  • However, the predictive capability of allometry is limited for low clearance compounds, a requirement for oral drug candidates, as it does not account for species differences in metabolism. (europeanpharmaceuticalreview.com)
  • We therefore also tested the hypothesis that the extraction ratio influences the consequence of altered hepatic metabolism of these opioids. (duke.edu)
  • CYP3A inhibition decreases alfentanil clearance more than fentanyl clearance, confirming that the extraction ratio influences the consequence of altered hepatic drug metabolism. (duke.edu)
  • A reduced rate of lidocaine metabolism following tumescent liposuction may result from an inhibition of cytochrome P450 3A4 (CYP3A4) by sertraline (Zoloft) and flurazepam (Dalmane). (liposuction.com)
  • Since 1994 there has been a rapid expansion of information about the specificity of hepatic microsomal enzymes of the cytochrome P450 family for the metabolism of different drugs. (liposuction.com)
  • In order to circumvent the first-pass effect, the authors continue to explain that a drug normally undergoes rapid hepatic metabolism could be administered parenterally to bypass the liver in order to reach therapeutic effect before being metabolized. (nursingassignmentowl.com)
  • In Burchum & Rosenthal (2021), they explain that the rates of hepatic drug metabolism tend to decline with advanced age, and alternations in receptor properties may underlie altered sensitivity to some medications. (nursingassignmentowl.com)
  • In Patel et al (2022), warfarin is hepatic metabolism, primarily through the CYP2C9 enzyme. (nursingassignmentowl.com)
  • Explain the hepatic drug metabolism of children 1 year and older. (nursingassignmentowl.com)
  • How do they compare with the hepatic drug metabolism of infants and adults? (nursingassignmentowl.com)
  • As Burchum & Rosenthal (2021) explain, hepatic drug metabolism of children 1 year and older is similar to those in adults, but the metabolize drugs rate are faster than adults until age two years then gradually declines. (nursingassignmentowl.com)
  • So, increase or reduction in dosing interval may be needed for drugs that are eliminated by hepatic metabolism. (nursingassignmentowl.com)
  • Unlike children one year older and adults, the authors state that the drug-metabolizing capacity of newborns is low, so neonates are especially sensitive to drugs that are eliminated majorly by hepatic metabolism. (nursingassignmentowl.com)
  • Overall hepatic metabolism of many drugs through the cytochrome P-450 enzyme system decreases with age. (msdmanuals.com)
  • Animal research suggests that GBE is non-mutagenic, non-teratogenic, and that it does not illicit organ damage or impairment of renal or hepatic function. (restorativemedicine.org)
  • The pharmacokinetic behaviour of a drug depends on the animal physiology (i.e., renal and hepatic function, organ perfusion. (vin.com)
  • Renal and hepatic impairment. (azurewebsites.net)
  • Paroxetine is an established perpetrator of drug-drug interactions (DDIs) when coadministered with agents whose clearance is largely dependent on the activity of cytochrome P450 2D6 (CYP2D6). (aspetjournals.org)
  • Saxagliptin and, to a lesser extent, sitagliptin are largely metabolized by hepatic cytochrome P450 (CYP) 3A4 and 3A5 isoforms. (nih.gov)
  • Methods: Using a specific inhibitor of phosphoinositide 3-kinase α (PI3Kα), which effectively inhibits the insulin signaling pathway, we examined the effects of various β-adrenoceptor agonists, including the physiological endogenous agonist norepinephrine on glucose uptake and respiration in mouse brown adipocytes in vitro and on glucose clearance in mice in vivo. (monash.edu)
  • Paroxetine produced a concentration- and time-dependent inhibition of human liver microsomal CYP2D6 activity in vitro, as measured by dextromethorphan O -demethylation rate. (aspetjournals.org)
  • Additionally, in vitro experimental approaches and scaling strategies have been successfully applied to the quantitative prediction of in vivo clearance via glucuronidation and drug-drug interaction potential. (nih.gov)
  • Determining metabolic clearance from human in vitro tissue preparations such as hepatocytes and scaling to the whole body has been successfully used for several years. (europeanpharmaceuticalreview.com)
  • Monitor serum paracetamol levels in patients with hepatic disease during prolonged use. (azurewebsites.net)
  • An elevated arterial or free venous serum ammonia level is the classic laboratory abnormality reported in patients with hepatic encephalopathy. (medscape.com)
  • In particular, the availability of substrate and inhibitor "probes" for the major hepatic drug metabolizing UGTs together with batteries of recombinant enzymes allow the reaction phenotyping of drug glucuronidation reactions. (nih.gov)
  • Simvastatin (sim" va stat' in) is an orally available inhibitor of hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the major rate-limiting enzyme in cholesterol synthesis. (nih.gov)
  • Coadministration with these agents may cause increases in simvastatin levels and potentiate its hepatic or muscle toxicity. (nih.gov)
  • It presents with hepatic toxicity after long-term use of oral diazepam due to the first-pass effect. (nursingassignmentowl.com)
  • Acute respiratory distress, metabolic acidosis, and death after rapid infusion of intravenous lipid emulsions have been reported. (drugs.com)
  • The newer antidepressant selective serotonin reuptake inhibitors (SSRI) such as sertraline are metabolized by the hepatic enzymes CYP3A4 and CYP2D6. (liposuction.com)
  • Insulin resistance strongly influences sustained response rates, at least in genotype-1 patients. (isciii.es)
  • Insulin resistance decreases during and after treatment in patients that achieved virus C clearance. (isciii.es)
  • The treatment of insulin resistance by decreasing hyperinsulinemia could improve sustained response rates in patients with chronic hepatitis C treated with peginterferon plus ribavirin. (isciii.es)
  • Insulin resistance is a major feature of the metabolic syndrome. (isciii.es)
  • Besides, virus C infection may induce insulin resistance by blocking intracellular signaling, and lastly, insulin resistance has been associated with a decreased rate of sustained response to peginterferon alpha plus ribavirin in patients with chronic hepatitis C. (isciii.es)
  • The insulin resistance/metabolic syndrome is characterised by the variable coexistence of hyperinsulinaemia, obesity, dyslipidaemia, and hypertension. (nihatodabasi.com)
  • Also, HMG-CoA-reductase inhibitors cause secondary up-regulation of hepatic LDL receptors, with increased LDL-cholesterol clearance and reduction of both total and LDL cholesterol in the serum. (wikipedia.org)
  • Hepatorenal syndrome is diagnosed when a creatinine clearance rate of less than 40 mL/min is present or when a serum creatinine level of greater than 1.5 mg/dL, a urine volume of less than 500 mL/day, and a urine sodium level of less than 10 mEq/L are present. (medscape.com)
  • The exogenous infusion of a maximally stimulating dose of epinephrine (1 μg · min -1 · kg -1 ) into saline-infused control animals for 3 h produced a marked hyperglycemia that resulted from a sustained increase in the rate of hepatic glucose production and a reduction in the metabolic clearance rate for glucose. (psu.edu)
  • These results indicate that EtOH alters hepatic glucose production in response to epinephrine. (psu.edu)
  • Hepatic glucose production was determined basally and throughout the euglycemic clamp study. (northwestern.edu)
  • 0.05) residual hepatic glucose production occurred during the euglycemic clamp in the polycystic ovary syndrome women. (northwestern.edu)
  • Adverse carbohydrate and lipid metabolic effects: Monitor glucose in prediabetic and diabetic women taking CAMRESE. (nih.gov)
  • The former did not correlate with in vivo clearance (12.9 ml/min/kg) for digoxin. (aspetjournals.org)
  • Intrinsic clearances ( V max / K m ) of compounds are often calculated using microsome incubations in an effort to predict in vivo hepatic clearances. (aspetjournals.org)
  • We hypothesize that hepatic transporters present in hepatocytes, but not in microsomes, are often the missing link explaining such discrepancies between microsome data and in vivo profiles. (aspetjournals.org)
  • Furthermore, β-adrenoceptor mediated glucose clearance in vivo did not require insulin or Akt activation but was attenuated upon administration of a β 3 -adrenoceptor antagonist. (monash.edu)
  • We conclude that the interplay of transporters and enzymes must be considered in defining the intrinsic metabolic clearance of the liver and in evaluating potential drug-drug interactions. (aspetjournals.org)
  • The metabolic clearance estimated from microsomes was 4.59 ± 0.69 ml/min/kg. (aspetjournals.org)
  • There was no metabolic difference for NQ in male and female mice, rat or human liver microsomes. (biomedcentral.com)
  • Studies using rat and human liver microsomes demonstrated that the rate of formation of AMT and GAMT increased in the presence of NADPH, suggesting the involvement of a NADPH-dependent enzyme system. (aspetjournals.org)
  • Transjugular Intrahepatic Portosystemic Shunt (TIPS) is an established procedure for the complications of portal hypertension, such as variceal bleeding, refractory ascites and hepatic hydrothorax. (bvsalud.org)
  • The central role of DMPK in drug discovery is to contribute to the optimisation of compounds for man by balancing the properties associated with drug gastrointestinal absorption (for orally delivered therapies), distribution, clearance, elimination and DDI potential as rapidly and cost effectively as possible. (europeanpharmaceuticalreview.com)
  • Cerivastatin is metabolized via the hepatic pathway. (wikipedia.org)
  • Pathway defects in lipoprotein synthesis, processing, and clearance can lead to accumulation of atherogenic lipids in plasma and endothelium. (nihatodabasi.com)
  • Glucoregulation during low- and moderate-intensity exercise is primarily mediated by an increase in the portal venous glucagon-to-insulin ratio ( 1 ), which stimulates hepatic glucose output, maintaining euglycemia largely through a feedback mechanism ( 2 - 4 ) that matches the increment to the increased requirements. (diabetesjournals.org)
  • These soft spots are locations on the molecule particularly susceptible to metabolic modification, which can contribute to high pharmacokinetic clearance. (chromatographyonline.com)
  • With the exception of the primary hydroxylated metabolite of saxagliptin, which is 2-fold less potent than its parent molecule, metabolic products of hepatic biotransformation are minimally active and none appreciably contribute to either the therapeutic or the toxic effects of DPP-4 inhibitors. (nih.gov)
  • Clearances were reduced to 12% (0.64 +/- 0.25 ml. kg-1. (duke.edu)
  • The first is the identification of major metabolites, which provides medicinal chemists with information on the metabolic 'soft spots. (chromatographyonline.com)
  • Hepatic, to principal metabolites, ethisterone and 17-hydroxymethylethisterone. (drugbank.com)
  • As with other rapidly acting intravenous anesthetic agents, the half-time of the blood-brain equilibration is approximately 1 minute to 3 minutes, accounting for the rate of induction of anesthesia. (guidelinecentral.com)
  • Table 2 lists the typical unintended pregnancy rates for users of combination oral contraceptives and other methods of contraception. (rxlist.com)
  • Correct and consistent use of methods can result in lower failure rates. (rxlist.com)
  • METHODS: Practitioners from 13 French- speaking countries were invited to answer an online questionnaire on the hepatic hydrothorax diagnosis and its management. (bvsalud.org)
  • As a consequence, the YF vaccination coverage rate, which was 5% of the population in 2016, increased to 65% by the end of 2018 in the metropolitan area of the city of São Paulo. (cdc.gov)
  • Common signs and symptoms may stem from decreased hepatic synthetic function (eg, coagulopathy), portal hypertension (eg, variceal bleeding), or decreased detoxification capabilities of the liver (eg, hepatic encephalopathy). (medscape.com)
  • The two main pharmacokinetic parameters are clearance and volume of distribution. (vin.com)
  • Magnitudes of interactions produced by paroxetine (20-30 mg/day) with desipramine, risperidone, perphenazine, atomoxetine, ( S )-metoprolol, and ( R )-metoprolol were predicted, considering the contribution of CYP2D6 to their oral clearance. (aspetjournals.org)
  • The hyperinsulinemic state induces several abnormalities in the liver, endothelium, and kidneys, and is the main feature in the metabolic syndrome. (isciii.es)
  • Thus, insulin concentrations are usually high early in type-2 diabetes, but have also been seen in many subjects who are not obese or diabetic, but who have other metabolic syndrome components such as hypertriglyceridemia or arterial hypertension (1). (isciii.es)
  • Metabolic studies in humans have demonstrated that 3'-azido-3'-deoxythymidine (AZT) is primarily eliminated as its 5'-O-glucuronide (GAZT). (aspetjournals.org)
  • Objective: β-adrenoceptor mediated activation of brown adipose tissue (BAT) has been associated with improvements in metabolic health in models of type 2 diabetes and obesity due to its unique ability to increase whole body energy expenditure, and rate of glucose and free fatty acid disposal. (monash.edu)
  • Even premature neonates undergoing surgery can mount a clinically significant stress response, as measured by hormonal and metabolic indicators. (medscape.com)
  • If spontaneous ventilation is maintained, the major cardiovascular effect is arterial hypotension (sometimes greater than a 30% decrease) with little or no change in heart rate and no appreciable decrease in cardiac output. (guidelinecentral.com)
  • For certain drugs, like phenylbutazone in dogs or salicylate in cats, the elimination is dose-dependent due to saturation of the process at high concentrations, and clearance cannot be considered constant beyond a certain level. (vin.com)
  • The concept of clearance is extremely useful for dosage adjustment because at the typical therapeutic doses, the systemic clearance of a drug is usually constant over the interval of plasma concentrations of clinical importance. (vin.com)
  • Hepatic injury (in doses higher then recommended), anaphylaxis. (azurewebsites.net)
  • DIPRIVAN is a single access parenteral product (single patient infusion vial) which contains 0.005% disodium edetate (EDTA) to inhibit the rate of growth of microorganisms, for up to 12 hours, in the event of accidental extrinsic contamination. (guidelinecentral.com)
  • The aims of this article are which follows: To gather the practices of hepatogastroenterologists or pulmonologists practitioners regarding the diagnosis and management of the hepatic hydrothorax. (bvsalud.org)
  • Computed tomography (CT) scanning and MRI studies of the brain may be important in ruling out intracranial lesions when the diagnosis of hepatic encephalopathy is in question. (medscape.com)
  • A brief review is made of the role of insulin in satiety and in the control of body weight, and of the newly available techniques to accurately quantify secretion, hepatic extraction, and post-hepatic delivery rates of insulin. (blogspot.com)
  • Metabolic drug clearance is determined from the ratio of two independent kinetic parameters: V max and K m . (aspetjournals.org)
  • As β-adrenoceptor agonist administration results in increased hepatic gluconeogenesis that can consequently result in secondary pancreatic insulin release, there is uncertainty regarding the importance of insulin and the subsequent activation of its downstream effectors in mediating β-adrenoceptor stimulated glucose uptake in BAT. (monash.edu)
  • In addition, there is enhanced cortisol clearance by A-ring reductases, (notably 5α-reductase). (endocrine-abstracts.org)
  • Cerivastatin mainly acts by competitively inhibiting HMG-CoA-reductase, which is the rate-limiting enzyme step in cholesterol biosynthesis. (wikipedia.org)
  • Quantitative clearance of the parent was measured using the full-scan data. (chromatographyonline.com)
  • Certain measurements are used to determine the amount of liver cells indirectly by measuring metabolic function or drug clearance as a substitute for quantitative liver function. (hindawi.com)
  • Metabolic and hormonal indicators of the degree of stress a surgical patient has can be monitored during and after surgery. (medscape.com)
  • Traditional hepatic function tests including indicators for hepatocellular injury (aminotransferase levels), biliary tract injury (alkaline phosphatase, gamma glutamyl transpeptidase, and total bilirubin), and functional synthesis (albumin, urea, glucose, and prothrombin time) are routinely checked in patients on HD [ 1 ]. (hindawi.com)
  • Due to the competition, the rate of mevalonate production by the enzyme is reduced. (wikipedia.org)
  • However, no detailed cellular metabolic studies have been reported on the complete catabolic fate of AZT at the hepatic site. (aspetjournals.org)
  • Complex relationships between rates of receptor binding and dissociation appear to strongly influence the durations of action of those DPP-4 inhibitors with comparatively shorter half-lives. (nih.gov)
  • They may be normal even when active hepatic injury occurs in patients with azotemia or ESRD [ 2 , 3 ] or be elevated falsely due to injury in other organs. (hindawi.com)
  • Opioid effects were determined by pupillometry, respiratory rate, and Visual Analog Scale scores. (duke.edu)
  • If no untoward reactions occur, the infusion rate can be increased to 1 ml/minute. (rxlist.com)