In vitro identification of metabolites of verapamil in rat liver microsomes

Acta Pharmacologica Sinica

Volumn 25, Issue 1, 2004, Pages 121-128

  Sun, Lu ^a   Zhang, Shu Qiu ^a   Zhong, Da Fang ^a  

^a SHENYANG PHARMACEUTICAL UNIVERSITY   (China)

Author keywords

High pressure liquid chromatography; In vitro metabolism; Liver microsomes; Mass spectrometry; Verapamil

Indexed keywords

DRUG METABOLITE; N,O DINORVERAPAMIL; O NORVERAPAMIL; UNCLASSIFIED DRUG; VERAPAMIL;

ANIMAL TISSUE; ARTICLE; CONCENTRATION RESPONSE; DEALKYLATION; DRUG METABOLISM; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IN VITRO STUDY; ISOMER; LIQUID CHROMATOGRAPHY; LIVER MICROSOME; MASS SPECTROMETRY; NONHUMAN; RAT; ULTRACENTRIFUGATION;

ANIMALS; BIOTRANSFORMATION; CALCIUM CHANNEL BLOCKERS; MALE; MICROSOMES, LIVER; RATS; RATS, WISTAR; VERAPAMIL;

EID: 0347654950     PISSN: 16714083     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (19)

1. Toffoli G, Simone F, Corona G, Raschack M, Cappelletto B, Gigante M, et al. Structure-activity relationship of verapamil analogs and reversal of multidrug resistance. Biochem Pharmacol 1995; 50: 1245-55.
2. Pauli-Magnus C, von Richter O, Burk O, Ziegler A, Mettang T, Eichelbaum M, et al. Characterization of the major metabolites of verapamil as substrates and inhibitors of P-glycoprotein 1. J Pharmacol Exp Ther 2000; 293: 376-82.
3. 14C]verapamil in man. Drug Metab Dispos 1979; 7: 145-8.
4. Mikus G, Eichelbaum M, Fischer C, Gumulka S, Klotz U, Kroemer HK. Interaction of verapamil and cimetidine: Stereochemical aspects of drug metabolism, drug disposition and drug action. J Pharmacol Exp Ther 1990; 253: 1042-8.
5. Walles M, Thum T, Levsen K, Borlak J. Verapamil metabolism in distinct regions of the heart and in cultures of cardiomyocytes of adult rats. Drug Metab Dispos 2001; 29: 761-8.
6. Tracy TS, Korzekwa KR, Gonzalez FJ, Wainer IW. Cytochrome P450 isoforms involved in metabolism of the enantiomers of verapamil and norverapamil. Br J Clin Pharmacol 1999; 47: 545-52.
7. Kroemer HK, Gautier JC, Beaune P, Henderson C, Wolf CR, Eichelbaum M. Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn-Schmiedebergs Arch Pharmacol 1993; 348: 332-7.
8. Busse D, Cosme J, Beaune P, Kroemer HK, Eichelbaum M. Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn-Schmiedebergs Arch Pharmacol 1995; 353: 116-21.
9. Neugebauer G. Comparative cardiovascular actions of verapamil and its major metabolites in the anesthetized dog. Cardiovasc Res 1978; 12: 247-54.
10. Johnson KE, Balderston SM, Pieper JA, Mann DE, Reiter MJ. Electrophysiologic effects of verapamil metabolites in the isolated heart. J Cardiovasc Pharmacol 1991; 17: 830-7.
11. Nelson WL, Olsen LD, Beitner DB, Pallow RJ. Regio-chemistry and substrate stereoselectivity of O-demethylation of verapamil in the presence of the microsomal fraction from rat and human liver. Drug Metab Dispos 1988; 16: 184-8.
12. Nelson WL, Olsen LD. Regiochemistry and enantioselectivity in the oxidative N-dealkylation of verapamil. Drug Metab Dispos 1988; 16: 834-41.
13. Vogelgesang B, Echizen H, Schmidt E, Eichelbaum M. Stereoselective first-pass metabolism of highly cleared drugs studies of the bioavailability of L- and D-verapamil examined with a stable isotope technique. Br J Clin Pharmacol 1984; 18: 733-40.
14. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265-75.
15. Omura T, Sato R. The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J Biol Chem 1964; 239: 2370-8.
16. Zhong DF, Zhang SQ, Sun L, Zhao XY. Metabolism of roxithromycin in phenobarbital-treated rat liver microsomes. Acta Pharmacol Sin 2002; 23: 455-60.
17. Lu AH, Shu Y, Huang SL, Wang W, Ou-yang DS, Zhou HH. In vitro proguanil activation to cycloguanil is mediated by CYP2C19 and CYP3A4 in adult Chinese liver microsomes. Acta Pharmacol Sin 2000; 21: 747-52.
18. Liu XQ, Zhao Y, Li D, Qiao ZY, Wang GJ. Metabolism and metabolic inhibition of cilnidipine in human liver microsomes. Acta Pharmacol Sin 2003; 24: 263-8.
19. Rodrigues D. Use of in vitro human metabolism studies in drug development. Biochem Pharmacol 1994; 48: 2147-56.