Portal de Periódicos da CAPES

Prediction of Xenobiotic Metabolism by Non‐Invasive Methods

1990; Wiley; Volume: 67; Issue: 2 Linguagem: Inglês

10.1111/j.1600-0773.1990.tb00793.x

1600-0773

Steffen Loft, Henrik E. Poulsen,

Metabolomics and Mass Spectrometry Studies

Pharmacology & ToxicologyVolume 67, Issue 2 p. 101-108 Free Access Prediction of Xenobiotic Metabolism by Non-Invasive Methods Steffen Loft, Steffen Loft Department of Pharmacology, University of Copenhagen, Juliane Mariesvej 20, DK-2100 Copenhagen Ø, and Department of Medicine A, Rigshospitalet, Blegdamsvej, DK-2100 Copenhagen Ø, DenmarkSearch for more papers by this authorHenrik Enghusen Poulsen, Corresponding Author Henrik Enghusen Poulsen* To whom correspondence should be directedSearch for more papers by this author Steffen Loft, Steffen Loft Department of Pharmacology, University of Copenhagen, Juliane Mariesvej 20, DK-2100 Copenhagen Ø, and Department of Medicine A, Rigshospitalet, Blegdamsvej, DK-2100 Copenhagen Ø, DenmarkSearch for more papers by this authorHenrik Enghusen Poulsen, Corresponding Author Henrik Enghusen Poulsen* To whom correspondence should be directedSearch for more papers by this author First published: August 1990 https://doi.org/10.1111/j.1600-0773.1990.tb00793.xCitations: 12AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References Andreasen, P. B., L. Ranek, B. E. Statland & N. Tygstrup: Clearance of antipyrine - dependence of quantitative liver function. Eur. J. Clin. Invest. 1974, 4, 129– 134. Atiba, J. O., G. Taylor, R. A. Pershe & T. F. Blaschke: Plasma antipyrine half-life can be determined from urine data. Brit. J. Clin. Pharmacol. 1987, 23, 715– 719. Bachmann, K., J. Schwartz, R. Forney & L. Jauregui: Phenytoin as a probe of drug metabolism. Predicting clearance with a single salivary sample. Pharmacology 1985, 30, 145– 152. Bachmann, K., J. Schwartz, T. Sullivan & L. Jauregui: Single sample estimate of ethosuximide clearance. Int. J. Clin. Pharmacol. Therap. Toxicol. 1986, 24, 546– 550. Bachmann, K., C. Yang, D. Jahn & J. Schwartz: The use of single sample clearance estimates to probe hepatic drug metabolism in rats. I. Xenobiotica 1988, 18, 151– 159. Bertilsson, L., T. K. Henthorn, E. Sanz, G. Tybring, J. Säwe & T. Villén: Importance of genetic factors in the regulation of diazepam metabolism: relationship to S-mephenytoin, but not debrisoquine, hydroxylation phenotype. Clin. Pharmacol. Therap. 1989, 45, 348– 355. Bingham, S. A. & J. H. Cummings: The use of creatinine as a check for the completeness of 24-hour urine collection. Hum. Nutr. Clin. Nutr. 1985, 39, 343– 353. Bock, K. W., J. Wilfang, R. Blume, D. Ullrich & J. Bircher: Paracetamol as a test drug to determine glucuronide formation in man. Effect of inducers and of smoking. Eur. J. Clin. Pharmacol. 1987, 31, 677– 683. Bobbis, A. R., M. J. Brodie, G. C. Kahn, E.-L. Toverud, I. A. Blair, S. Murray & D. S. Davies: Comparison of the in vivo and in vitro rates of formation of the three main metabolites and antipyrine in man. Brit. J. Clin. Pharmacol. 1981, 12, 771– 777. Brüch, M., L. Kling, W. Legrum & E. Maser: The 14CO2 breath test: facilities and limitations of a rapid and noninvasive method for in vivo evaluation of modified hepatic cytochrome P-450 - a critique. Arch. Toxicol. 1987, 60, 81– 85. Brøsen, K. & L. F. Gram: Clinical significance of the sparteine/debrisoquine oxidation polymorphism. Eur. J. Clin. Pharmacol. 1989, 36, 537– 547. Campbell, M. E., D. M. Grant, T. Inaba & W. Kalow: Biotransformation of caffeine, paraxanthine, theophylline, and theobromine by polycyclic aromatic hydrocarbon-inducible cytochrome(s) P-450 in human liver microsomes. Drug Metab. Dispos. 1987a, 15, 237– 249. Campbell, M. E., S. P. Spielberg & W. Kalow: A urinay metabolite ratio that reflects systemic caffeine clearance. Clin. Pharmacol. Therap. 1987b, 42, 157– 165. Capel, I. D., M. Jenner, M. H. Pinnock, H. M. Dorell & D. C. Williams: The effect of isolation stress on some hepatic drug and carcinogen metabolizing enzymes in rats. J. Environ. Pathol. Toxicol. 1980, 3, 337– 344. Caporaso, N., R. B. Hayes, M. Dosemeci, R. Hoover, R. Ayesh, M. Hetzel & J. Idle: Lung cancer risk, occupational exposure, and the debrisoquine metabolic phenotype. Cancer Res. 1989, 49, 3675– 3679. Chindavijac, B., F. M. Belpaire, F. De Smet & M. G. Bogaert: Alteration of the pharmacokinetics of propranolol and antipyrine elicited by indwelling catheters in the rat. J. Pharmacol. Exp. Therap. 1988, 246, 1075– 1979. Clark, D. W. J.: Genetically determined variability in acetylation and oxidation - therapeutic implications. Drugs 1985, 29, 342– 375. Critchley, J. A. J. H., G. R. Nimmo, C. A. Gregson, N. M. Wool-house & L. F. Prescott: Inter-subject and ethnic differences in paracetamol metabolism. Brit. J. Clin. Pharmacol. 1986, 22, 649– 657. Døssing, M.: Antipyrine clearance during occupational exposure to styrene. Brit. J. Indust. Med. 1983, 40, 224– 228. Døssing, M., Aa. Vølund & H. E. Poulsen: Optimal sampling times for minimum variance of clearance determination. Brit. J. Clin. Pharmacol. 1983, 15, 231– 235. Døssing, M., H. E. Poulsen, P. B. Andreasen & N. Tygstrup: A simple method for determination of antipyrine clearance. Clin. Pharmacol. Therap. 1982, 32, 392– 396. Eichelbaum, M., N. Spannbrucker, B. Steincke & H. J. Dengler: Defective N-oxidation of sparteine in man: a new pharmacogenetic defect. Eur. J. Clin. Pharmacol. 1979, 16, 183– 187. Emery, P., S. P. Panayi, G. Huston, K. I. Welsh, S. C. Mitchell, R. L. Smith & R. H. Waring: D-penicillamine induced toxicity in rheumatoid arthritis: the role of sulphoxidation status and HLA-DR3. J. Rheumatol. 1984, 11, 626– 632. Ged, G., J. M. Rouillon, L. Pichard, J. Combalbert, N. Bressot, P. Bories, H. Michel, P. Beaune & P. Maurel: The increase in urinary excretion of 6β-hydroxycortisol as a marker of human hepatic cytochrome P45OIIIA induction. Brit. J. Clin. Pharmacol. 1989, 28, 373– 387. Gonzalez, F. J.: The molecular biology of cytochrome P45Os. Pharmacol. Rev. 1988, 40, 243– 288. Grant, D. M., B. K. Tang & W. Kalow: Variability in caffeine metabolism. Clin. Pharmacol. Therap. 1983, 33, 591– 602. Grant, D. M., B. K. Tang & W. Kalow: A simple test for acetylator phenotype using caffeine. Brit. J. Clin. Pharmacol. 1984, 17, 459– 464. Grant, D. M., B. K. Tang, M. E. Campbell & W. Kalow: Effect of allopurinol on caffeine disposition in man. Brit. J. Clin. Pharmacol. 1986, 21, 454– 458. Guengerich, F. P.: Roles of cytochrome P-450 enzymes in chemical carcinogenesis and cancer chemotherapy. Cancer Res. 1988, 48, 2946– 2954. Hein, D. W.: Acetylator genotype and arylamine-induced carcinogenesis. Biochem. Biophy. Acta 1988, 948, 37– 66. Hepner, G. W. & E. S. Vesell: Assessment of aminopyrine metabolism in man after oral administration of 14C-aminopyrine. Effects of phenobarbital, disulfiram and portal cirrhosis. New Engl. J. Med. 1974, 291, 1384– 1388. Hepner, G. W., E. S. Vesell, A. Lipton, H. A. Harvey & G. R. Wilkinson: Disposition of aminopyrine, antipyrine, diazepam, and indocyanine green in patients with liver disease or on anticonvulsant drug therapy: diazepam breath test and correlations in drug elimination. Clin. Pharmacol. Therap. 1977, 90, 440– 456. Hutchings, A. D., R. D. Monie, B. P. Spragg & P. A. Routledge: Saliva and plasma concentrations of isoniazid and acetylisoniazid in man. Brit. J. Clin. Pharmacol. 1988, 25, 585– 589. Hvidberg, E. F.: Ethnic differences in phenytoin kinetics. In: Ethnic differences in reaction to drugs and xenobiotics. Eds.: W. Kalow, H. W. Goedde & D. P. Agarwal. Alan R. Liss, Inc. New York 1986, pp. 279– 287. Inaba, T. & T. D. Arias: On phenotyping with isoniazed: the use of urinary acetylation ratio and the uniqueness of antimodes. Study of two Amerindian populations. Clin. Pharmacol. Therap. 1987, 42, 493– 497. Irving, C. S., A. Dale, N. Kanichi, A. L. Baker & P. D. Klein: The aminopyrine breath test as a measure of liver function. A quantitative description of its metabolic basis in normal subjects. J. Lab. Clin. Med. 1982, 100, 356– 373. Jackson, P. R., G. T. Tucker, M. S. Lennard & H. F. Woods: Polymorphic drug oxidation: pharmacokinetic basis and comparison of experimental indices. Brit. J. Clin. Pharmacol. 1986, 22, 541– 550. Jacqz, E., S. D. Hall, R. A. Branch & G. R. Wilkinson: Polymorphic metabolism of mephenytoin in man: pharmacokinetic interaction with a co-regulated substrate, mephobarbital. Clin. Pharmacol. Therap. 1986a, 39, 646– 653. Jacqz, E., S. Ward, R. Johnson, S. Schenker, J. Gerkens & R. A. Branch: Extrahepatic glucuronidation of morphine in the dog. Drug. Metab. Dispos. 1986b, 14, 627– 630. Kalow, W.: Genetic variation in the human hepatic cytochrome P-450 system. Eur. J. Clin. Pharmacol. 1987, 31, 633– 641. Kamali, F., J. R. Fry & G. D. Bell: Salivary secretion of paracetamol in man. J. Pharm. Pharmacol. 1987, 39, 150– 152. Kellermann, G., J. R. Jett, M. Luyten-Kellermann, H. L. Moses & R. S. Fontana: Variation of microsomal mixed function oxidase(s) and human lung cancer. Cancer 1980, 45, 1438– 1442. Knodell, R. G., R. K. Dubey, G. R. Wilkinson & F. P. Guengerich: Oxidative metabolism of hexobarbital in human liver: relationship of polymorphic S-mephenytoin-4-hydroxylation. J. Pharmacol. Exp. Therap. 1988, 245, 845– 849. Knutti, R., H. Rothweiler & C. H. Schlatter: Effect of pregnancy on the pharmacokinetics of caffeine. Eur. J. Clin. Pharmacol. 1981, 21, 121– 126. Kronbach, T., V. Fisher & U. A. Meyer: Cyclosporine metabolism in human liver: identification of a cytochrome P-45OIII gene family as the major cyclosporine-metabolizing enzyme explains interactions of cyclosporine with other drugs. Clin. Pharmacol. Therap. 1988, 43, 630– 635. Küpfer, A. & R. Preisig: Pharmacogenetics of mephenytoin: a new drug hydroxylation polymorphism in man. Eur. J. Clin. Pharmacol. 1984, 26, 753– 759. Lauterburg, B. & J. Bircher: Hepatic microsomal drug metabolizing capacity measured in vivo by breath analysis. Gastroenterology 1973, 65, 556– 559. Legrum, W., L. Kling & E. Funke: Radioisomers of scoparone (6,7-dimethoxycoumarin) as a tool for in vivo differentiation of various hepatic monooxygenase inducers in mice using the breath test technique. J. Pharmacol. Exp. Therap. 1984, 228, 769– 773. Loft, S. & H. E. Poulsen: Metabolism of metronidazole and antipyrine in isolated rat hepatocytes: influence of sex and enzyme induction and inhibition. Biochem. Pharmacol. 1989, 38, 1125– 1136. Loft, S., J. Sonne, H. E. Poulsen, K. T. Petersen, B. G. Jørgensen & M. Døssing: Inhibition and induction of metronidazole and antipyrine metabolism. Eur. J. Clin. Pharmacol. 1987, 32, 35– 41. Loft, S., H. E. Poulsen, J. Sonne & M. Døssing: Metronidazole clearance: a one sample method and influencing factors. Clin. Pharmacol. Therap. 1988, 43, 420– 428. Lucey, M. R., J. C. Kolars, R. M. Merion, D. A. Campbell, M. Aldrich & P. B. Watkins: Cyclosporin toxicity at therapeutic blood levels and cytochrome P-450 IIIA. Lancet 1990, 335, 11– 15. Mahgoub, A., J. R. Idle, L. G. Dring, R. Lancaster & R. L. Smith: Polymorphic hydroxylation of debrisoquine in man. Lancet 1977, ii, 584– 586. McGourty, J. C., J. H. Silas, M. S. Lennard, G. T. Tucker & H. F. Woods: Metoprolol metabolism and debrisoquine oxidation polymorphism - population and family studies. Brit. J. Clin. Pharmacol. 1985, 20, 555– 566. Mitchell, S. C., R. H. Waring, C. S. Haley, J. R. Idle & R. L. Smith: Genetic aspects of the polymodally distributed sulfoxidation of S-carboxymethyl-L-cysteine in man. Brit. J. Clin. Pharmacol. 1984, 18, 507– 521. Nebert, D. W., D. R. Nelson, M. Adesnik, M. J. Coon, R. W. Estabrook, F. J. Gonzalez, F. P. Guengerich, I. C. Gunsalus, E. F. Johnson, B. Kemper, W. Levin, I. R. Phillips, R. Sato & M. R. Waterman: The P450 superfamily: updated listing of all genes and recommended nomenclature for the chromosomal loci. DNA 1989, 8, 1– 14. Ohnhaus, E. E., A. M. Breckenridge & B. K. Park: Urinary excretion of 6β-hydroxycortisol and the time course measurement of enzyme induction in man. Eur. J. Clin. Pharmacol. 1989, 36, 39– 46. Olomu, A. B., C. R. Vickers, R. H. Warning, D. Clements, C. Babbs, T. W. Warnes & E. Elias: High incidence of poor sulfoxidation in patients with primary biliary cirrhosis. New Engl. J. Med. 1988, 318, 1089– 1092. Park, B. K.: Assessment of the drug metabolism capacity of the liver. Brit. J. Clin. Pharmacol. 1982, 14, 631– 651. Penno, M. B. & E. S. Vesell: Monogenic control of variations in antipyrine metabolite formation. J. Clin. Invest. 1983, 71, 1698– 1709. Poulsen, H. E. & H. Pilsgaard: One sample antipyrine clearance after 90% partial hepatectomy in rats. Liver 1985, 5, 200– 204. Poulsen, H. E. & S. Loft: Antipyrine as a model drug to study hepatic drug metabolizing capacity. J. Hepatol. 1988, 6, 374– 382. Prescott, L. F.: Kinetic and metabolism of paracetamol and phenacetin. Brit. J. Clin. Pharmacol. 1980, 10, 291S– 298S. Price, V. F. & D. J. Jollow: Mechanism of decreased acetaminophen glucuronidation in the fasted rat. Biochem. Pharmacol. 1988, 37, 1067– 1075. Raucy, J. L., J. M. Lasker, C. S. Lieber & M. Black: Acetaminophen activation by human liver cytochromes P45OIIEI and P45OIA2. Arch. Biochem. Biophys. 1989, 271, 270– 283. Rhodes, J. C. & J. B. Houston: Antipyrine metabolite kinetics in rats: studies on dose and time dependence. Biopharm. Drug. Dispos. 1983, 4, 125– 135. Ritschel, W. A. & P. Thompson: Monitoring of drug concentrations in saliva: a non-invasive pharmacokinetic procedure. Meth. Find. Exp. Clin. Pharmacol. 1983, 5, 511– 525. Saenger, P.: 6β-Hydroxycortisol in random urine samples as an indicator of enzyme induction. Clin. Pharmacol. Therap. 1983, 34, 818– 821. Scadding, G. K., R. Ayesh, J. Brostoff, S. C. Mitchell, R. H. Waring & R. L. Smith: Poor sulphoxidation ability in patients with food sensitivity. Brit. Med. J. 1988, 297, 105– 107. Schellens, J. H. M., J. H. F. van der Wart, M. Danhof, E. A. van der Velse & D. D. Breimer: Relationship between the metabolism of antipyrine, hexobarbital and theophylline in man as assessed by a 'cocktail' approach. Brit. J. Clin. Pharmacol. 1988, 26, 373– 384. Schmid, B., J. Bircher, R. Preisig & A. Küpfer: Polymorphic dextromethorphan metabolism: co-segregation of oxidative O-demethylation with debrisoquine hydroxylation. Clin. Pharmacol. Therap. 1985, 38, 618– 624. Schoeller, D. A., A. L. Kotake, G. L. Lambert, P. S. Krager & A. L. Baker: Comparison of the phenacetin and aminopyrine breath tests: effect of liver disease, inducers and cobaltous chloride. Hepatology 1985, 5, 276– 281. Sesardic, D., A. R. Boobis, R. J. Edwards & D. S. Davies: A form of cytochrome P450 in man, ortologous to form d in the rat, catalyses and O-deethylation of phenacetin and is inducible by cigarette smoking. Brit. J. Clin. Pharmacol. 1988, 26, 363– 372. Shimada, T., M. Iwasaki, M. V. Martin & F. P. Guengerich: Human liver microsomal cytochrome P-450 enzymes involved in the bio-activations of procarcinogens detected by umu gene response in Salmonella typhimurium TA 1535/pSK1002. Cancer Res. 1989, 49, 3218– 3228. Slattery, J. T., J. M. Wilson, T. F. Kalhorn & S. D. Nelson: Dose-dependent pharmokinetics of acetaminophen: evidence of glutathione depletion in humans. Clin. Pharmacol. Therap. 1987, 41, 413– 418. Slusher, L. B., S. S. Park, H. V. Gelboin & E. S. Vesell: Studies on the metabolism of amimopyrine, antipyrine and theophylline using monoclonal antibodies to cytochrome P-450 isozymes purified from rat liver. Biochem. Pharmacol. 1987, 14, 2359– 2367. Steiner, E., G. Alván, M. Garle, J. H. Maguire, M. Lind, S.-O. Nilson, T. Tomson, J. S. McClanahan & F. Sjöqvist: The debrisoquine hydroxylation phenotype does not predict the metabolism of phenytoin. Clin. Pharmacol. Therap. 1987, 42, 326– 33. Steventon, G. A. C. Williams, R. H. Waring & H. S. Pall: Xenobiotic metabolism in motoneuron disease. Lancet 1988, ii, 644– 647. Sultatos, L. G., B. H. Dvorchic, E. S. Vesell, D. G. Shand & R. A. Branch: Further observations on relationship between antipyrine half-life, clearance and volume of distribution: an appraisal of alternative kinetic parameters used to assess the elimination of antipyrine. Clin. Pharmacokin. 1980, 5, 263– 273. Svensson, C. K.: Is blood sampling for determination of antipyrine pharmacokinetics in heatlhy volunteers ethically justified Clin. Pharmacol. Therap. 1988, 44, 365– 368. Tang, B. K., D. Kadar & W. Kalow: An alternative test for acetylator phenotyping with caffeine. Clin. Pharmacol. Therap. 1987, 42, 509– 513. Teunissen, M. W. E., D. Kampf, I. Roots, N. P. E. Vermeulen, D. D. Breimer: Antipyrine metabolite formation in patients with chronic renal failure. Eur. J. Clin. Pharmacol. 1985a, 28, 589– 595. Teunissen, M. W. E., L. G. J. De Leede, J. K. Boeijiinga & D. D. Breimer: Correlation between antipyrine and theophylline metabolism in man after simultaneous single dose administration and at steady state. J. Pharmacol. Exp. Therap. 1985b, 233, 770– 775. Toverud, E.-L., A. R. Boobis, M. J. Brodie, S. Murrray, P. N. Bennett, V. Whitmarsh & D. S. Davies: Differential induction of antipyrine metabolism. Eur. J. Clin. Pharmacol. 1981, 21, 155– 160. Trnavska, Z., V. Rejholec, J. Elis & V. Spicak: Comparative pharmacokinetic analysis of theophylline in serum and saliva. Int. J. Clin. Pharmacol. Res. 1987, 7, 329– 335. Van Dyke, R. A., K. L. Koistra, C. J. Moses & G. Powis: Effect of inhalation anesthetics on antipyrine pharmacokinetics of mice. Biochem. Pharmacol. 1987, 36, 1023– 1027. Ward, S. A., T. Walle, U. K. Walle, G. R. Wilkinson & R. A. Branch: Propranolol's metabolism is determined by both me- phenytoin and debrisoquine hydroxylase activities. Clin. Pharmacol. Therap. 1989, 45, 72– 79. Waring, R. H., S. C. Mitchell, J. O'Gorman & M. Fraser: Cytosolic sulphoxidation of S-carboxymethyl-L-cysteine in mammals. Biochem. Pharmacol. 1986, 35, 2999– 3002. Watkins, P. B. S. A. Murray, L. G. Winkelman, D. M. Heuman, S. A. Wrighton & P. S. Guzelian: Erythromycin breath test as an assay of glucocorticoid inducible liver cytochromes P-450: studies in rats and patients. J. Clin. Invest. 1989, 83, 688– 697. Waxman, D. J., C. Attisano, F. P. Guengerich & D. P. Lapenson: Human liver microsomal steroid metabolism: identification of the major microsomal steroid hormone 6β-hydroxylase cytochrome P-450 enzyme. Arch. Biochem. Biophys. 1988, 37, 71– 81. Wedlund, P. J., W. S. Aslanian, C. B. McAllister, G. R. Wilkinson & R. A. Branch: Mephenytoin hydroxylation deficiency in Caucasians: frequency of a new oxidative drug metabolism polymorphism. Clin. Pharmacol. Therap. 1984, 36, 773– 780. Vesell, E. S.: The antipyrine test in clinical pharmacology: conceptions and misconceptions. Clin. Pharmacol. Therap. 1979, 26, 275– 286. Vesell, E. S., G. T. Passananti, P. A. Glenwright & B. H. Dvorchik: Studies on the disposition of antipyrine, aminopyrine and phenacetin using plasma, saliva and urine. Clin. Pharmacol. Therap. 1975, 18, 259– 272. Wietholtz, H., M. Voegelin, M. J. Arnaud, J. Bircher & R. Preisig: Assessment of the cytochrome P-448 dependent liver enzyme system by a caffeine breath test. Eur. J. Clin. Pharmacol. 1981, 21, 53– 59. Wilkinson, G. R., F. P. Guengerich & R. A. Branch: Genetic polymorphism of S-mephenytoin hydroxylation. Pharmacol. Therap. 1989, 43, 53– 76. Wilkinson, G. R.: Clearance approaches in pharmacology. Pharmacol. Rev. 1987, 39, 1– 47. Villeneuve, J.-P., C. Infate-Rivard, M. Ampelas, G. Pomier-Layrargues, P.-M. Huet & D. Marleau: Prognostic value of the aminopyrine breath test in cirrhotic patients. Hepatology 1986, 6, 928– 931. Wilson, V. L., R. E. Larson & M. J. Moldowan: A non-invasive method for the study of hepatic drug metabolism in rodents: antineoplastic drug effects on antipyrine metabolism in mice. Chem.-Biol. Inter. 1982, 40, 159– 168. Yue, Q. Y., J-O, Svenson, C. Alm, F. Sjöqvist & J. Säwe: Interindividual and interethnic differences in the demethylation and glucuronidation of codeine. Brit. J. Clin. Pharmacol. 1989a, 28, 629– 637. Yue, Q. Y., J-O. Svenson, C. Alm, F. Sjöqvist & J. Säwe: Codeine-O-demethylation cosegregates with polymorphic debrisoquine hydroxylation. Brit. J. Clin. Pharmacol. 1989b, 28, 639– 645. Zanger, U. M., F. Vilbois, J. P. Hardwick & U. A. Meyer: Absence of hepatic cytochrome P450bufl causes genetically deficient debrisoquine oxidation in man. Biochemistry 1988, 27, 5447– 5454. Citing Literature Volume67, Issue2August 1990Pages 101-108 ReferencesRelatedInformation