Citrus paradisi: A plant species of the genus CITRUS, family RUTACEAE that produces the familiar grapefruit. There is evidence that grapefruit inhibits CYTOCHROME P-450 CYP3A4, resulting in delayed metabolism and higher blood levels of a variety of drugs.Food-Drug Interactions: The pharmacological result, either desirable or undesirable, of drugs interacting with components of the diet. (From Stedman, 25th ed)Citrus: A plant genus of the family RUTACEAE. They bear the familiar citrus fruits including oranges, grapefruit, lemons, and limes. There are many hybrids which makes the nomenclature confusing.Beverages: Liquids that are suitable for drinking. (From Merriam Webster Collegiate Dictionary, 10th ed)Carbolines: A group of pyrido-indole compounds. Included are any points of fusion of pyridine with the five-membered ring of indole and any derivatives of these compounds. These are similar to CARBAZOLES which are benzo-indoles.Psoralens: Linear furanocoumarins which are found in many PLANTS, especially UMBELLIFERAE and RUTACEAE, as well as PSORALEA from which they were originally discovered. They can intercalate DNA and, in an UV-initiated reaction of the furan portion, alkylate PYRIMIDINES, resulting in PHOTOSENSITIVITY DISORDERS.Cytochrome P-450 CYP3A: A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.Flavanones: A group of FLAVONOIDS characterized with a 4-ketone.Felodipine: A dihydropyridine calcium antagonist with positive inotropic effects. It lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels.Rosales: An order of the ANGIOSPERMS, subclass Rosidae. Its members include some of the most known ornamental and edible plants of temperate zones including roses, apples, cherries, and peaches.Biological Availability: The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.Oxidoreductases, N-DemethylatingCross-Over Studies: Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed)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.Area Under Curve: A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)Gastric Juice: The liquid secretion of the stomach mucosa consisting of hydrochloric acid (GASTRIC ACID); PEPSINOGENS; INTRINSIC FACTOR; GASTRIN; MUCUS; and the bicarbonate ion (BICARBONATES). (From Best & Taylor's Physiological Basis of Medical Practice, 12th ed, p651)Acebutolol: A cardioselective beta-1 adrenergic antagonist with little effect on the bronchial receptors. The drug has stabilizing and quinidine-like effects on cardiac rhythm, as well as weak inherent sympathomimetic action.Citrus sinensis: A plant species of the genus CITRUS, family RUTACEAE that provides the familiar orange fruit which is also a source of orange oil.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.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.Hesperidin: A flavanone glycoside found in CITRUS fruit peels.Medicine, Kampo: System of herbal medicine practiced in Japan by both herbalists and practitioners of modern medicine. Kampo originated in China and is based on Chinese herbal medicine (MEDICINE, CHINESE TRADITIONAL).Herb-Drug Interactions: The effect of herbs, other PLANTS, or PLANT EXTRACTS on the activity, metabolism, or toxicity of drugs.Schisandra: A plant genus of the family SCHISANDRACEAE. Members contain schisandrins (Russian) which are also called gomisins (Japanese) or wuweizins (Chinese). The compounds in this genus are very similar to those in the related KADSURA and medicinal usage is very similar. It is sometimes adulterated with KADSURA.Quinidine: An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.Saquinavir: An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases, and also inhibits CYTOCHROME P-450 CYP3A.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Fruit: The fleshy or dry ripened ovary of a plant, enclosing the seed or seeds.Coumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.Cisapride: A substituted benzamide used for its prokinetic properties. It is used in the management of gastroesophageal reflux disease, functional dyspepsia, and other disorders associated with impaired gastrointestinal motility. (Martindale The Extra Pharmacopoeia, 31st ed)Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.Plant Extracts: Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.Caco-2 Cells: Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells, such as ENTEROCYTES. These cells are valuable in vitro tools for studies related to intestinal cell function and differentiation.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.Limonins: A group of degraded TRITERPENES in which the four terminal carbons of the C17 side chain have been removed, and the remaining portion often forming C17 furans.P-Glycoprotein: A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).Midazolam: A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.Purinergic P2Y Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2Y RECEPTORS. Included under this heading are antagonists for specific P2Y receptor subtypes.Organic Anion Transporters: Proteins involved in the transport of organic anions. They play an important role in the elimination of a variety of endogenous substances, xenobiotics and their metabolites from the body.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Intestinal Absorption: Uptake of substances through the lining of the INTESTINES.Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Aflatoxin B1: A potent hepatotoxic and hepatocarcinogenic mycotoxin produced by the Aspergillus flavus group of fungi. It is also mutagenic, teratogenic, and causes immunosuppression in animals. It is found as a contaminant in peanuts, cottonseed meal, corn, and other grains. The mycotoxin requires epoxidation to aflatoxin B1 2,3-oxide for activation. Microsomal monooxygenases biotransform the toxin to the less toxic metabolites aflatoxin M1 and Q1.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)Carbamates: Derivatives of carbamic acid, H2NC(=O)OH. Included under this heading are N-substituted and O-substituted carbamic acids. In general carbamate esters are referred to as urethanes, and polymers that include repeating units of carbamate are referred to as POLYURETHANES. Note however that polyurethanes are derived from the polymerization of ISOCYANATES and the singular term URETHANE refers to the ethyl ester of carbamic acid.Cyclosporine: A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).Amiodarone: An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Amlodipine: A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of ANGINA PECTORIS and HYPERTENSION.Anthelmintics: Agents destructive to parasitic worms. They are used therapeutically in the treatment of HELMINTHIASIS in man and animal.Anti-Arrhythmia Agents: Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.HIV Protease Inhibitors: Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly.Pulse: The rhythmical expansion and contraction of an ARTERY produced by waves of pressure caused by the ejection of BLOOD from the left ventricle of the HEART as it contracts.Metabolic Clearance Rate: Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.Anticholesteremic Agents: Substances used to lower plasma CHOLESTEROL levels.Terfenadine: A selective histamine H1-receptor antagonist devoid of central nervous system depressant activity. The drug was used for ALLERGY but withdrawn due to causing LONG QT SYNDROME.Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.
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