Kinetic characterization and identification of the enzymes responsible for the hepatic biotransformation of adinazolam and N-desmethyladinazolam in man

Journal of Pharmacy and Pharmacology

Volumn 50, Issue 3, 1998, Pages 265-274

  Venkatakrishnan, Karthik ^a   Von Moltke, Lisa L ^a   Duan, Su Xiang ^a   Fleishaker, Joseph C ^b   Shader, Richard I ^a   Greenblatt, David J ^a  

^a TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 NAPHTHOQUINONE; ADINAZOLAM; COMPLEMENTARY DNA; CYTOCHROME P450; DIETHYLDITHIOCARBAMIC ACID; KETOCONAZOLE; LIVER ENZYME; N DESMETHYLADINAZOLAM; OMEPRAZOLE; QUINIDINE; SULFAPHENAZOLE; TROLEANDOMYCIN; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DEMETHYLATION; DRUG TRANSFORMATION; HUMAN; HUMAN TISSUE; LIVER METABOLISM; LIVER MICROSOME; LYMPHOBLASTOID CELL; MICHAELIS CONSTANT;

EID: 0031952437     PISSN: 00223573     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.2042-7158.1998.tb06859.x     Document Type: Article

References (12)

1. Crespi, C. L. (1995) Xenobiotic-metabolizing human cells as tools for pharmacological and toxicological research. Adv. Drug Res. 26: 179-235
2. Fleishaker, J. C., Phillips, J. P. (1989) Adinazolam pharmacokinetics and behavioral effects following administration of 20-60 mg doses of its mesylate salt in healthy volunteers. Psychopharmacology 99: 34-39
3. Fleishaker, J. C., Smith, T. C., Friedman, H. L., Hulst, L. K. (1992a) Separation of the pharmacokinetic/pharmacodynamic properties of oral and i.v. adinazolam mesylate and N-desmethyladinazolam mesylate in healthy volunteers. Drug Invest. 4: 155-165
4. Fleishaker, J. C., Hulst, L. K., Smith, T. C., Friedman, H. L. (1992b) Clinical pharmacology of adinazolam and N-desmethyladinazolam mesylate following single intravenous infusions of each compound in healthy volunteers. Eur. J. Clin. Pharmacol. 42: 287-294
5. Ko, J.-W., Sukhowa, N., Thacker, D., Chen, P., Flockhart, D. A. (1997) Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms. Drug Metab. Dispos. 25: 853-862
6. Newton, D. J., Wang, R. W., Lu, A. Y. H. (1995) Cytochrome P450 inhibitors. Evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab. Dispos. 23: 154-158
7. Schmider, J., Greenblatt, D. J., von Moltke, L. L., Harmatz, J. S., Shader, R. I. (1995) N-Demethylation of amitriptyline in vitro: role of cytochrome P-450 3A (CYP3A) isoforms and effect of metabolic inhibitors. J. Pharmacol. Exp. Ther. 275: 592-597
8. Sethy, V. H., Collins, R. J., Daniels, E. G. (1984) Determination of biological activity of adinazolam and its metabolites. J. Pharm. Pharmacol. 36: 546-548
9. Shimada, T., Yamazaki, S., Mimura, M., Inui, Y., Guengerich, F. P. (1994) Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J. Pharmacol. Exp. Ther. 270: 414-423
10. Ueng, Y.-F., Kuwabara, T., Chun, Y.-J., Guengerich, F. P. (1997) Cooperativity in oxidations catalysed by cytochrome P450 3A4. Biochemistry 36: 370-381
11. von Moltke, L. L., Greenblatt, D. J., Harmatz, J. S., Shader, R. I. (1993) Alprazolam metabolism in vitro: studies of human, monkey, mouse, and rat liver microsomes. Pharmacology 47: 268-276
12. von Moltke, L. L., Greenblatt, D. J., Cotreau-Bibbo, M. M., Duan, S. X., Harmatz, J. S., Shader, R. I. (1994) Inhibition of desipramine hydroxylation in vitro by serotonin reuptake inhibitor antidepressants, and by quinidine and ketoconazole: a model system to predict drug interaction in vivo. J. Pharmacol. Exp. Ther. 268: 1278-1283