Zolpidem metabolism in vitro: Responsible cytochromes, chemical inhibitors, and in vivo correlations

British Journal of Clinical Pharmacology

Volumn 48, Issue 1, 1999, Pages 89-97

  Von Moltke, Lisa L ^a   Greenblatt, David J ^a   Granda, Brian W ^a   Su, X D ^a   Grassi, Jeffrey M ^a   Venkatakrishnan, Karthik ^a   Harmatz, Jerold S ^a   Shader, Richard I ^a  

^a TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cytochromes P450; Drug interactions; In vitro metabolism; Ketoconazole; Zolpidem

Indexed keywords

ANTIFUNGAL AGENT; BENZODIAZEPINE RECEPTOR STIMULATING AGENT; CYTOCHROME; DRUG METABOLITE; KETOCONAZOLE; SULFAPHENAZOLE; SULFONAMIDE; ZOLPIDEM;

ARTICLE; DRUG CLEARANCE; DRUG METABOLISM; DRUG TRANSFORMATION; HUMAN; HUMAN TISSUE; LIVER CLEARANCE; LIVER MICROSOME; LYMPHOBLASTOID CELL; PRIORITY JOURNAL;

BIOTRANSFORMATION; CYTOCHROME P-450 ENZYME SYSTEM; ENZYME INHIBITORS; HUMANS; HYPNOTICS AND SEDATIVES; KETOCONAZOLE; METABOLIC CLEARANCE RATE; MICROSOMES, LIVER; PYRIDINES; TRANSFECTION; TUMOR CELLS, CULTURED;

EID: 0032986686     PISSN: 03065251     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1365-2125.1999.00953.x     Document Type: Article

References (52)

1. 1 Nowell PD, Mazumdar S, Buysse DJ, et al. Benzodiazepines and zolpidem for chronic insomnia: a meta-analysis of treatment efficacy. JAMA 1997; 278: 2170-2176.
2. 2 Roth T, Puech AJ, Paiva T. Zolpidem - place in therapy. In Zolpidem: an Update of its Pharmacological Properties and Thereapeutic Place in the Management of Insomnia, eds H. Freeman, A. J. Puech, T. Roth. Paris: Elsevier, 1996: 215-230.
3. 3 Hochns JD, Perry PJ. Zolpidem: a nonbenzodiazepine hypnotic for treatment of insomnia. Clin Pharm 1993; 12: 814-828.
4. 4 Langtry HD, Benfield P. Zolpidem: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential. Drugs 1990; 40: 291-313.
5. 5 Sanger DJ, Benavides J, Perrault G, et al. Recent developments in the behavioral pharmacology of benzodiazepine receptors: evidence for the functional significance of receptor subtypes. Neurosci Biobehav Rev 1994; 18: 355-372.
6. 6 Byrnes JJ, Greenblatt DJ, Miller LG. Benzodiazepine receptor binding of non-benzodiazepines in vivo: alpidem, zolpidem, and zopiclone. Brain Res Bull 1992; 29: 905-908.
7. 7 Salvà P, Costa J. Clinical pharmacokinetics and pharmacodynamics of zolpidem: therapeutic implications. Clin Pharmacokin 1995; 29: 142-153.
8. 8 Durand A, Thénot JP, Bianchetti G, et al. Comparative pharmacokinetic profile of two imidazopyridine drugs: zolpidem and alpidem. Drug Metab Rev 1992; 24: 239-166.
9. 9 Ascalone V, Flaminio L, Guinebault P, et al. Determination of zolpidem, a new sleep-inducing agent, and its metabolites in biological fluids: pharmacokinetics, drug metabolism and overdosing investigations in humans. J Chromatogr 1992; 581: 237-250.
10. 10 Hempel G, Blaschke G. Direct determination of zolpidem and its main metabolites in urine using capillary electrophoresis with laser-induced flourescence detection. J Chromatogr B 1996; 675: 131-137.
11. 11 Pichard L, Gillet G, Bonfils C, et al. Oxidative metabolism of zolpidem by human liver cytochrome P450s. Drug Metab Dispos 1995; 23: 1253-1262.
12. 12 Venkatakrishnan K, Greenblatt DJ, von Moltke LL, et al. Five distinct human cytochromes mediate amitriptyline N-demethylation in vitro: dominance of CYP 2C19 and 3A4. J Clin Pharmacol 1998; 38: 112-121.
13. 13 Venkatakrishnan K, von Moltke LL, Greenblatt DJ. Relative quantities of catalytically active CYP 2C9 and 2C19 in human liver microsomes: application of the relative activity factor approach. J Pharm Sci 1998; 87: 845-853.
14. 14 Crespi CL. Xenobiotic-metabolizing human cells as tools for pharmacological and toxicological research. Adv Drug Res 1995; 26: 179-235.
15. 15 Crespi CL, Penman BW. Use of cDNA expressed human cytochrome P450 enzymes to study potential drug-drug interactions. Adv Pharmacol 1997; 43: 171-188.
16. 16 von Moltke LL, Greenblatt DJ, Cotreau-Bibbo MM, et al. Inhibition of desipramine hydroxylation in vitro by serotonin-reuptake-inhibitor antidepressants, and by quinidine and ketoconazole: a model system to predict drug interactions in vivo. J Pharmacol Exp Ther 1994; 268: 1278-1283.
17. 17 von Moltke LL, Greenblatt DJ, Cotreau-Bibbo MM, et al. Inhibitors of alprazolam metabolism in vitro: effect of serotonin-reuptake-inhibitor antidepressants, ketoconazole and quinidine. Br J Clin Pharmacol 1994; 38: 23-31.
18. 18 von Moltke LL, Greenblatt DJ, Harmatz JS, et al. Triazolam biotransformation by human liver microsomes in vitro: effects of metabolic inhibitors, and clinical confirmation of a predicted interaction with ketoconazole. J Pharmacol Exp Ther 1996; 276: 370-379.
19. 19 Schmider J, Greenblatt DJ, Harmatz JS, et al. Enzyme kinetic modeling as a tool to analyse the behaviour of cytochrome P450 catalysed reactions: application to amitriptyline N-demethylation. Br J Clin Pharmacol 1996; 41: 593-604.
20. 20 von Moltke LL, Greenblatt DJ, Grassi JM, et al. Protease inhibitors as inhibitors of human cytochromes P450: high risk associated with ritonavir. J Clin Pharmacol 1998; 38: 106-111.
21. 21 Shimada T, Yamazaki H, Mimura M, et al. 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 1994; 270: 414-423.
22. 22 Greenblatt DJ, von Moltke LL, Harmatz JS, et al. Kinetic and dynamic interaction study of zolpidem with ketoconazole, itraconazole, and fluconazole. Clin Pharmacol Ther 1998; 64: 661-671.
23. 23 Newton DJ, Wang RW, Lu AYH. Cytochrome P450 inhibitors: evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab Dispos 1995; 23: 154-158.
24. 24 von Moltke LL, Greenblatt DJ, Duan SX, et al. Inhibition of triazolam hydroxylation by ketoconazole, itraconazole, hydroxyitraconazole and fluconazole in vitro. Pharmac Pharmacol Comm 1998; 4: 443-445.
25. 25 Elkins S, Ring BJ, Binkley SN, et al. Autoactivation and activation of the cytochrome P450s. Int J Clin Pharmacol Ther 1998; 36: 642-651.
26. 26 Korzekwa KR, Krishnamachary N, Shou, M, et al. Evaluation of Atypical Cytochrome P 450 kinetics with two-substrate models: evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites. Biochemistry 1998; 37: 4137-4147.
27. 27 Venkatakrishnan K, von Moltke LL, Greenblatt DJ. Human cytochromes P450 mediating phenacetin O-deethylation in vitro: validation of the high affinity component as an index of CYP1A2 activity. J Pharm Sci 1998; 87: 1502-1507.
28. 28 Greenblatt DJ, Wright CE, von Moltke LL, et al. Ketoconazole inhibition of triazolam and alprazolam clearance: differential kinetic and dynamic consequences. Clin Pharmacol Ther 1998; 64: 237-247.
29. 29 Olkkola K, Ahonen J, Neuvonen P. The effect of the systemic antimycotics, itraconazole and fluconazole, on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Anesthes Analges 1996; 82: 511-516.
30. 30 Varhe A, Olkkola KT, Neuvonen PJ. Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole or itraconazole. Clin Pharmacol Ther 1994; 56: 601-607.
31. 31 Varhe A, Olkkola KT, Neuvonen PJ. Fluconazole, but not terbinafine, enhances the effects of triazolam by inhibiting its metabolism. Br J Clin Pharmacol 1996; 41: 319-323.
32. 32 Olkkola KT, Backman JT, Neuvinen PJ. Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole. Clin Pharmacol Ther 1994; 55: 481-485.
33. 33 Luurila H, Kivistö KT, Neuvonen PJ. Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zolpidem. Eur J Clin Pharmacol 1998; 54: 336-340.
34. 34 Greenblatt DJ, von Moltke LL, Schmider J, et al. Inhibition of human cytochrome P; 450-3A isoforms by fluoxetine and norfluoxetine: in vitro and in vivo studies. J Clin Pharmacol 1996; 36: 792-798.
35. 35 Wright CE, Lasher-Sisson TA, Steenwyk RC, et al. A pharmacokinetic evaluation of the combined administration of triazolam and fluoxetine. Pharmacotherapy 1992; 12: 103-106.
36. 36 Piergies AA, Sweet J, Johnson M, et al. The effect of co-administration of zolpidem with fluoxetine: pharmacokinetics and pharmacodynamics. Int J Clin Pharmacol Ther 1996; 34: 178-183.
37. 37 Allard S, Sainati S, Roth-Schechter B, et al. Minimal interaction between fluoxetine and multiple-dose zolpidem in healthy women. Drug Metab Dispos 1998; 26: 617-622.
38. 38 Villikka K, Kivistö KT, Backman JT, et al. Triazolam is ineffective in patients taking rifampin. Clin Pharmacol Ther 1997; 61: 8-14.
39. 39 Villikka K, Kivistö KT, Luurila H, et al. Rifampin reduces plasma concentrations and effects of zolpidem. Clin Pharmacol Ther 1997; 62: 629-634.
40. 40 Backman JT, Olkkola KT, Neuvonen PJ. Rifampin drastically reduces plasma concentrations and effects of oral midazolam. Clin Pharmacol Ther 1996; 59: 7-13.
41. 41 Tucker GT. The rational selection of drug interaction studies: implications of recent advances in drug metabolism. Int J Clin Pharmacol Ther Toxicol 1992; 30: 550-553.
42. 42 Boobis AR. Prediction of inhibitory drug-drug interactions by studies in vitro. In Advances in Drug Metabolism in Man eds Pacifici GM, Fracchia GN. Luxembourg, the European Commission., 1995: 513-539.
43. 43 Leemann TD, Dayer P. Quantitative prediction of in vivo drug metabolism and interactions from in vitro data. In Advances in Drug Metabolism in Man, eds Pacifici GM, Fracchia GN. The European Commission, Luxembourg., 1995: 783-830.
44. 44 Rodrigues AD, Wong SL. Application of human liver microsomes in metabolism based drug-drug interations: in vitro-in vivo correlations and the Abbott Laboratories experience. Adv Pharmacol 1997; 43: 65-101.
45. 45 Bertz RJ, Granneman GR. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clin Pharmacokin 1997; 32: 210-258.
46. 46 von Moltke LL, Greenblatt DJ, Schmider J, et al. Metabolism of drugs by Cytochrome P450, 3A isoforms: implications for drug interactions in psychopharmacology. Clin Pharmacokin 1995 29(Suppl 1): 33-43.
47. 47 von Moltke LL, Greenblatt DJ, Schmider J, et al. In vitro approaches to predicting drug interactions in vivo. Biochem Pharmacol 1998; 55: 113-122.
48. 48 Greenblatt DJ, von Moltke LL. Can in vitro models predict drug interactions in vivo? A review of methods, problems, and successes. In: Drug-Drug Interactions: Analyzing in Vitro-in Vivo Correlations Ed W Hori Southboro, MA, International Business Communications 1997 2.2.1-.2.2.28.
49. 49 Ito K, Iwatsubo T, Kanamitsu S, et al. Quantitative prediction of in vivo drug clearance and drug interactions from in vitro data on metabolism, together with binding and transport. Ann Rev Pharmacol Toxicol 1998; 38: 461-499.
50. 50 Heykants J, Michiels M, Meuldermans W, et al. The pharmacokinetics of itraconazole in animals and man: an overview. In Recent Trends in the Discovery, Development and Evaluation of Antifungal Agents ed Fromtling R. J.R. Prous, Barcelona. Science Publishers, 1987: 223-249.
51. 51 Heykants J, van Peer A, van de Velde V, et al. The clinical pharmacokinetics of itraconazole: an overview. Mycoses 1989; 32(Suppl 1): 67-87.
52. 52 Obach RS. Nonspecific binding to microsomes. Drug Metab Dispos 1997; 25: 1359-1369.