Tolterodine, a new muscarinic receptor antagonist, is metabolized by cytochromes P450 2D6 and 3A in human liver microsomes

Drug Metabolism and Disposition

Volumn 26, Issue 4, 1998, Pages 289-293

  Postlind, Hans ^a   Danielson, Åsa ^a   Lindgren, Anders ^a   Andersson, Stig H G ^a  

^a Pharmacia and Upjohn AB ^*

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450 ISOENZYME; MUSCARINIC RECEPTOR BLOCKING AGENT; TOLTERODINE;

ARTICLE; CONTROLLED STUDY; DEALKYLATION; DRUG DETERMINATION; DRUG OXIDATION; ENZYME ACTIVITY; HUMAN; HUMAN CELL; LIVER MICROSOME METABOLISM; PRIORITY JOURNAL; PROTEIN EXPRESSION;

ARYL HYDROCARBON HYDROXYLASES; BENZHYDRYL COMPOUNDS; CRESOLS; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 CYP3A; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; MICROSOMES, LIVER; MUSCARINIC ANTAGONISTS; OXIDOREDUCTASES, N-DEMETHYLATING; PHENYLPROPANOLAMINE;

STAPHYLOCOCCUS PHAGE 3A;

EID: 0031918465     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (20)

1. Baldwin SJ, Bloomer JC, Smith GJ, Ayrton AD, Clarke SE and Chenery RJ (1995) Ketoconazole and sulphaphenazole as the respective inhibitors of P4503A and 2C9. Xenobiotica 25:261-270.
2. Brynne N, Stahl MMS, Hallén B, Edlund PO, Palmér L, Höglund P and Gabrielsson J (1997) Pharmacokinetics and pharmacodynamics of tolterodine in man: A new drug for the treatment of urinary bladder overactivity. Int J Clin Pharmacol Ther 35:287-295.
3. Daly AK, Cholerton S, Gregory W and Idle JR (1993) Metabolic polymorphisms. Pharmacol Ther 57:129-160.
4. Guengerich FP (1990) Mechanism-based inactivation of human liver microsomal cytochrome P-450 IIIA4 by gestodene. Chem Res Toxicol 3:363-371.
5. Guengerich FP (1992) Characterization of human cytochrome P450 enzymes. FASEB J 6:745-748.
6. Guengerich FP and Shimada T (1991) Oxidation of toxic and cancerogenic chemicals by human cytochrome P450 enzymes. Chem Res Toxicol 4:391-407.
7. Guengerich FP, Müller-Enoch D and Blair IA (1986) Oxidation of quinidine by human liver cytochrome P-450. Mol Pharmacol 30:287-295.
8. Honig PK, Wortham DC, Zamani K, Conner DP, Mullin JC and Cantilena LR (1993) Terfenadine-ketoconazole interaction. Pharmacokinetic and electrocardiographic consequences. JAMA 269:1513-1518.
9. Inaba T, Jurima M, Mahon WA and Kalow W (1985) In vitro inhibition studies of two isozymes of human liver cytochrome P-450: Mephenytoin p-hydroxylase and sparteine monooxygenase. Drug Metab Dispos 13: 443-448.
10. Maurice M, Pichard L, Daujat M, Fabre I, Joyeux H, Domergue J and Maurel P (1992) Effects of imidazole derivatives on cytochrome P450 from human hepatocytes in primary culture. FASEB J 6:752-758.
11. Murray M (1992) P450 enzymes: in inhibition mechanisms, genetic regulation and effects of liver disease. Clin Pharmacokinet 23:132-146.
12. Nilvebrant L, Hallén B and Larsson G (1997) Tolterodine - a new bladder selective muscarinic receptor antagonist: Preclinical pharmacological and clinical data. Life Sci 60:1129-1136.
13. Periti P, Mazzei T, Mini E and Novelli A (1992) Pharmacokinetic drug interactions of macrolides. Clin Pharmacokinet 23:106-131.
14. Pichard L, Fahre I, Fabre G, Domergue J, Saint Aubert B, Mourad G and Maurel P (1990) Cyclosporin A drug interaction. Screening for inducers and inhibitors of cytochrome P450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and in liver microsomes. Drug Metab Dispos 18:595-606.
15. Schmid B, Bircher J, Preisig R and Kupfer A (1985) Polymorphic dextromethorphan metabolism: Co-segregation of oxidation of O-demethylation with debrisoquine hydroxylation. Clin Pharmacol Ther 38:618-624.
16. Smith RL (1986) Polymorphism in drug metabolism-implications for drug toxicity. Arch Toxicol 9(suppl):138-146.
17. Tassaneeyakul W, Brikett DJ, Veronese ME, McManus ME, Tukey RH, Quattrochi LC, Gelboin HV and Miners JO (1993) Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2. J Pharmacol Exp Ther 265:401-407.
18. Waxman DJ, Attisano C, Guengerich FP and Lapenson DP (1988) Human liver microsomal steroid metabolism: Identification of the major microsomal steroid hormone 6β-hydroxylase cytochrome P-450 enzyme. Arch Biochem Biophys 263:424-436.
19. Wienkers LC, Wurden CJ, Storch E, Kunze KL, Rettie AE and Trager WF (1996) Formation of (R)-8-hydroxywarfarin in human liver microsomes: a new metabolic marker of (S)-mephenytoin hydroxylase, P4502C19. Drug Metab Dispos 24:610-614.
20. Wrighton SA and Stevens JC (1992) The human hepatic cytochrome P450 involved in drug metabolism. Crit Rev Toxicol 22:1-21.