Cytochrome P-450 CYP1A2: A cytochrome P450 enzyme subtype that has specificity for relatively planar heteroaromatic small molecules, such as CAFFEINE and ACETAMINOPHEN.Kidney Papillary Necrosis: A complication of kidney diseases characterized by cell death involving KIDNEY PAPILLA in the KIDNEY MEDULLA. Damages to this area may hinder the kidney to concentrate urine resulting in POLYURIA. Sloughed off necrotic tissue may block KIDNEY PELVIS or URETER. Necrosis of multiple renal papillae can lead to KIDNEY FAILURE.Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Dealkylation: The removing of alkyl groups from a compound. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Debrisoquin: An adrenergic neuron-blocking drug similar in effects to GUANETHIDINE. It is also noteworthy in being a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism.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.Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.Pyuria: The presence of white blood cells (LEUKOCYTES) in the urine. It is often associated with bacterial infections of the urinary tract. Pyuria without BACTERIURIA can be caused by TUBERCULOSIS, stones, or cancer.IminesCytochrome 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.Salicylates: The salts or esters of salicylic acids, or salicylate esters of an organic acid. Some of these have analgesic, antipyretic, and anti-inflammatory activities by inhibiting prostaglandin synthesis.Analgesics, Non-Narcotic: A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.Acetonitriles: Compounds in which a methyl group is attached to the cyano moiety.Chlorzoxazone: A centrally acting central muscle relaxant with sedative properties. It is claimed to inhibit muscle spasm by exerting an effect primarily at the level of the spinal cord and subcortical areas of the brain. (From Martindale, The Extra Pharmacopoea, 30th ed, p1202)Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.Phenacetin: A phenylacetamide that was formerly used in ANALGESICS but nephropathy and METHEMOGLOBINEMIA led to its withdrawal from the market. (From Smith and Reynard, Textbook of Pharmacology,1991, p431)Hydroxylation: Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)Mexiletine: Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties.Aspirin: The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)Benzoflavones: Organic compounds containing a BENZENE ring attached to a flavone group. Some of these are potent arylhydrocarbon hydroxylase inhibitors. They may also inhibit the binding of NUCLEIC ACIDS to BENZOPYRENES and related compounds. The designation includes all isomers; the 7,8-isomer is most frequently encountered.Propafenone: An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity.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.KetonesAniline CompoundsFlutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species.Glucuronates: Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure.Methanol: A colorless, flammable liquid used in the manufacture of FORMALDEHYDE and ACETIC ACID, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness.Cytochrome P-450 CYP2D6: A cytochrome P450 enzyme that catalyzes the hydroxylation of many drugs and environmental chemicals, such as DEBRISOQUINE; ADRENERGIC RECEPTOR ANTAGONISTS; and TRICYCLIC ANTIDEPRESSANTS. This enzyme is deficient in up to 10 percent of the Caucasian population.Codon, Terminator: Any codon that signals the termination of genetic translation (TRANSLATION, GENETIC). PEPTIDE TERMINATION FACTORS bind to the stop codon and trigger the hydrolysis of the aminoacyl bond connecting the completed polypeptide to the tRNA. Terminator codons do not specify amino acids.Epoxy Compounds: Organic compounds that include a cyclic ether with three ring atoms in their structure. They are commonly used as precursors for POLYMERS such as EPOXY RESINS.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.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.Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.Oxidoreductases: The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)Kidney Diseases: Pathological processes of the KIDNEY or its component tissues.Nucleic Acids: High molecular weight polymers containing a mixture of purine and pyrimidine nucleotides chained together by ribose or deoxyribose linkages.Urinary Bladder: A musculomembranous sac along the URINARY TRACT. URINE flows from the KIDNEYS into the bladder via the ureters (URETER), and is held there until URINATION.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.Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.Mutagenicity Tests: Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests.Carcinogens: Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.Kinetics: The rate dynamics in chemical or physical systems.Benzoquinones: Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.Substance-Related Disorders: Disorders related to substance abuse.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.TritiumLiver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Sulfates: Inorganic salts of sulfuric acid.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.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.Homozygote: An individual in which both alleles at a given locus are identical.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.