Metabolism of anxiolytics and hypnotics: Benzodiazepines, buspirone, zoplicone, and zolpidem

Cellular and Molecular Neurobiology

Volumn 19, Issue 4, 1999, Pages 533-552

  Chouinard, Guy ^a,b   Lefko Singh, Karen ^c   Teboul, Eric ^d  

^a CENTRE DE RECHERCHE FERNAND SEGUIN   (Canada)

^b Allan Memorial Institute   (Canada)

^c UNIVERSITY OF ALBERTA   (Canada)

^d Hotel Dieu de S Jerome   (Canada)

Author keywords

Benzodiazepines; Conjugation; Cytochromes P450; Drug interactions; Oxidation; Reduction

Indexed keywords

ANTIVIRUS AGENT; ANXIOLYTIC AGENT; BENZODIAZEPINE DERIVATIVE; BUSPIRONE; CARBAMAZEPINE; CHLORPROMAZINE; CIMETIDINE; CYTOCHROME P450; ERYTHROMYCIN; FLUVOXAMINE; HALOPERIDOL; HYPNOTIC AGENT; ITRACONAZOLE; JOSAMYCIN; KETOCONAZOLE; LORAZEPAM; NEFAZODONE; NORFLUOXETINE; RANITIDINE; RITONAVIR; TRIAZOLAM; TRIMIPRAMINE; TROLEANDOMYCIN; UNINDEXED DRUG; ZOLPIDEM; ZOPICLONE;

CHEMICAL STRUCTURE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG HALF LIFE; DRUG INDICATION; DRUG METABOLISM; DRUG OXIDATION; PRIORITY JOURNAL; REVIEW;

ANTI-ANXIETY AGENTS; ANXIETY; BENZODIAZEPINES; BUSPIRONE; CYTOCHROME P-450 ENZYME SYSTEM; DRUG INTERACTIONS; HUMANS; HYPNOTICS AND SEDATIVES; PIPERAZINES; PYRIDINES;

EID: 0033017931     PISSN: 02724340     EISSN: None     Source Type: Journal    
DOI: 10.1023/A:1006943009192     Document Type: Review

References (99)

1. Abernethy, D. R., Greenblatt, D. J., and Shader, R. I. (1986). Benzodiazepine hypnotic metabolism: Drug interactions and clinical implications. Acta Psychiatr. Scand. 74 (Suppl. 332):32-38.
2. Allain, H., and Monti, J. (1997). General safety profile of zolpidem: Safety in elderly, overdose and rebound effects. Eur. Psychiatry 12 (Suppl. 1):21S-29S.
3. Amrein, R., Caro, J. P., Hartmann, D., et al. (1979). Clinical and psychometric effects of flunitrazepam during the day in relation to pharmacokinetic data. In Priest, R. G., Plestcher. A., and Ward, J. (eds.), Sleep Research, MTP Press, Lancaster, pp. 83-98.
4. Andersson, T., Miners, J. O., Veronese, M. E., and Birkett, D. J. (1994). Diazepam metabolism by human liver microsomes is mediated by both S-mephenytoin hydroxylase and CYP3A isoforms. J. Clin. Pharmacol. 38:131-137.
5. Aranko, K., Luurila, H., Backman, J. T., Neuvonen, P. J., and Olkkola, K. T. (1994). The effect of erythromycin on the pharmacokinetics and pharmacodynamics of zopiclone. J. Clin. Pharmacol. 38:363-367.
6. Bailey, D. G., Malcolm, J., Arnold, O., and Spence, J. D. (1998). Grapefruit juice-drug interactions. Br. J. Clin. Pharmacol. 46:101-110.
7. Baldessarini, R. J. (1985). Chemotherapy in Psychiatry: Principles and Practice, Harvard University Press, Cambridge, MA.
8. Barbhaiya, R. H., Shukla, U. A., Kroboth, P. D., and Greene, D. S. (1995). Coadministration of nefazodone and benzodiazepines. II A pharmacokinetic interaction study with triazolam. J. Clin. Psychopharmacol. 15:320-326.
9. Baumann, P. (1996). Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors. Clin. Pharmacokinet. 31:444-469.
10. Bertz. R. J., and Granneman, G. R. (1997). Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Drug Interact. 32:210-258.
11. Ciraulo, D. A., Shader, R. I., Greenblatt, D. J., and Creelman, W. L. (eds.) (1995). Drug Interactions in Psychiatry, 2nd Ed., Williams & Wilkins, Baltimore.
12. Colburn, W. F., and Jack, M. L. (1987). Relationships between CSF drug concentration receptor binding characteristics and pharmacokinetic and pharmacodynamic properties of selected 1,4 substituted benzodiazepines. Clin. Pharmacokinet. 12:179-190.
13. CPS (Compendium of Pharmaceuticals and Specialties), 24th ed. (1989). Canadian Pharmaceutical Association, Ottawa, Ontario
14. Cook, P. J. (1986). Benzodiazepine hypnotics in the elderly. Acta Psychiatr. Scand. 74 (Suppl. 332):149-158.
15. Cooper, A. J. (1982). Benzodiazepines: Towards more logical use. Scott. Med. J. 27:297-304.
16. Desager, J. P., Hulhoven, R., Harvengt, C., et al. (1988). Possible interaction between zolpidem, a new sleep inducer, and chlorpromazine, a phenothiazine neuroleptic. Psychopharmacology 96:63-66.
17. Dettli, L. (1986). Benzodiazepines in the treatment of sleep disorders: Pharmacokinetic aspects. Acta Psychiatr. Scand. 74 (Suppl. 332):9-19.
18. Divoll, M., Greenblatt, D. J., Ciraulo, D. A., Puri, S. K., Ho, I., and Shader, R. I. (1982). Clobazam kinetics: Intrasubject variability and effect of food on absorption. J. Clin. Pharmacol. 22:69-73.
19. Fernandez, C., Maradeix, V., Gimenez, F., Thuillier, A., and Farinotti, R. (1993). Pharmacokinetics of zopiclone and its enantiomers in Caucasian young healthy volunteers. Drug Metab. Disp. 21:1125-1128.
20. Fernandez, C., Martin, C., Gimenez, F., and Farinotti, R. (1995). Clinical pharmacokinetics of zopiclone. Clin. Pharmacokinet. 29:431-441.
21. Fleishaker, J. C., and Hulst, L. K. (1994). A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine. Eur. J. Pharmacol. 46:35-39.
22. Fulton, B., and Brogden, R. N. (1997). Buspirone - An updated review of its clinical pharmacology and therapeutic applications. CNS Drugs 7:68-88.
23. Gammans, R. E., Mayol, R. F., Mackenthum, Av., et al. (1985). The relationship between buspirone bioavailability and dose in healthy subjects. Biopharm. Disp. 6:139-145.
24. Gammans, R. E., Mayol, R. F., and Labudde, J. A. (1986). Metabolism and disposition of buspirone. Am. J. Med. 80 (Suppl. 3b): 41-51.
25. Gelenberg, A. J. (1983). Anxiety. In Bassuk, E. L., Schoonover, S. C., and Gelenberg, A. J. (eds.), The Practitioner's Guide to Psychoactive Drugs, 2nd ed., Plenum Press, New York.
26. Gillis, M. C. (ed.) (1997). Compendium of Pharmaceutical and Specialities, Canadian Pharmaceutical Association, Ottawa, Ontario, pp. 711-713.
27. Glue, P., and Banfield, C. (1996). Psychiatry, psychopharmacology and P-450s. Hum. Psychopharmacol. 11:97-114.
28. Gonzalez, F. J. (1992). Human cytochromes P450: problems and prospects. Trends Pharmacol. Sci. 13:346-352.
29. Greenblatt, D. J., and Shader, R. I. (1985). Clinical pharmacokinetics of the benzodiazepines. In Smith, D. E., and Wesson, D. R. (eds.), The Benzodiazepines: Current Standards for Medical Practice, MTP Press, Lancaster, PA.
30. Greenblatt, D. J., and Shader, R. I. (1986). Long-term administration of benzodiazepines: Pharmacokinetic versus pharmacodynamic tolerance. Psychopharmacol. Bull. 22:416-423.
31. Greenblatt, D. J., and Shader, R. I. (1987). The pharmacokinetics of ani-anxiety agents. In Meltzer, H. Y. (ed.), Psychopharmacology: The Third Generation of Progress, Raven Press: New York.
32. Greenblatt, D. J., Allen, M. D., MacLaughlin, D. R., Harmatz, J. S., and Sahder, R. I. (1978a). Diazepam absorption: effects of antacids and food. Clin. Pharmacol. Ther. 24:600-609.
33. Greenblatt, D. J., Woo, E., Allen, M. D., Orsulak, P. J., and Shader, R. I. (1978b). Rapid recovery from massive diazepam overdose. JAMA 240:1872-1874.
34. Greenblatt, D. J., Divoll, M., Harmatz, J. S., and Shader, R. I. (1982). Pharmacokinetic comparison of sublingual lorazepam with intravenous, intramuscular and oral lorazepam. J. Pharm. Sci. 71:248-252.
35. Greenblatt, D. J., Divoll, M., Abernethy, D. R., et al. (1983a). Benzodiazepine kinetics: Implications for therapeutics and pharmacogeriatrics. Drug Metab. Rev. 14:251-292.
36. Greenblatt, D. J., Shader, R. I., and Abernethy, D. R. (1983b). Current status of benzodiazepines (first of two parts). N. Engl. J. Med. 309:354-358.
37. Greenblatt, D. J., Shader, R. I., and Abernethy, D. R. (1983c). Current status of benzodiazepines (second of two parts). N. Engl. J. Med. 309:410-415.
38. Greenblatt, D. J., Abernethy, D. R., Morse, D. S., Harmatz, J. S., and Shader, R. I. (1984). Clinical importance of the interaction of diazepam and cimetidine. N. Engl. J. Med. 310:1639-1643.
39. Greenblatt, D. J., Friedman, H. L., and Shader, R. I. (1987). Correlating pharmacokinetics and pharmacodynamics of benzodiazepines: Problems and assumptions. Psychopharmacology 3:62-71.
40. Greenblatt, D. J., Preskorn, S. H., Cotreau, M. M., Horst, W. D., and Harmatz, J. S. (1992). Fluoxetine impairs clearance of alprazolam but not of clonazepam. Clin. Pharmacol. Ther. 52:479-486.
41. Greene, D. S., Salazar, D. E., Dockens, R. C., Kroboth, P., and Barbhaiya, R. H. (1995). Coadministration of nefazodone and benzodiazepines. III A pharmacokinetic interaction study with alprazolam. J. Clin. Psychopharmacol. 15:399-408.
42. Guengerich, F. P. (1990). Mechanism-based inactivation of human liver microsomal cytochrome P450 IIIA4 by gestodene. Chem. Res. Toxicol. 3:363-371.
43. Haefely, W., Kyburz, E., Gerecke, M., et al. (1985). Recent advances in the molecular pharmacology of benzodiazepine receptors and in the structure activity relationships of their agonists and antagonists. Adv. Drug Res. 14:165-332.
44. Hansten, P. D., and Horn, J. R. (1997). Drug Interactions, Analysis and Management, Applied Therapeutics, Vancouver, WA.
45. Harvey, A. T., and Preskorn, S. H. (1996a). Cytochrome P450 enzymes: Interpretation of their interactions with selective serotonin reuptake inhibitors. Part I. J. Clin. Psychopharmacol. 16:273-285.
46. Harvey, A. T., and Preskorn, S. H. (1996b). Cytochrome P450 enzymes: Interpretation of their interactions with selective serotonin reuptake inhibitors. Part II. J. Clin. Psychopharmacol, 16:345-354.
47. Harvey, S. C. (1985). Hypnotics and sedatives. In Goodman Gilman, A., Goodman, L. S., Dall, T. W., et al. (eds.), Goodman and Gilman's the Pharmacological Basis of Therapeutics, 7th ed., Macmillan, New York.
48. Hoehns, J. D., and Perry, P. J. (1993). Zolpidem: A nonbenzodiazepine hypnotic for treatment of insomnia. Clin. Pharm. 12:814-828.
49. Hollister, L. E. (1985). Principles of therapeutic applications of benzodiazepines. In Smith, D. E., and Wesson, D. R. (eds.), The Benzodiazepines: Current Standards for Medical Practice, MTP Press, Lancaster, PA, p. 87.
50. Hyman, S. E. (1988). Manual of Psychiatric Emergencies, 2nd ed., Little, Brown, Boston, p. 280.
51. Jajoo, H. K., Mayol, R. F., LaBudde, J. A., et al. (1989). Metabolism of the antianxiety drug buspirone in human subjects. Drug Metab. Dispos. 17:634-640.
52. Jochemsen, R., and Breimer, D. D. (1984). Pharmacokinetics of benzodiazepine hypnotics in man. PHIND Oct:244-248.
53. Kales, A., Soldates, C. R., and Vela-Bueno, A. (1985). Clinical comparison of benzodiazepine hypnotics with short and long elimination half-lives. In Smith, D. E., and Wesson, D. R. (eds.), The Benzodiazepines: Current Standards for Medical Practice, MTP Press, Lancaster, PA.
54. Klotz, U., Kargos, L., and Karto, J. (1980). Clinical pharmacokinetics of benzodiazepines. In Grobedder, H., Kahl, A. F., Klaus, W., et al. (eds.), Progress in Pharmacology, Vol. 3, Gustav Fischer Verly, Stuttgart.
55. Kroboth, P. D., Folan, M., Lush, R. M., Chaikin, P. C., Umesh, A., Shukla, A., Barbhaiya, R., and Salazar, D. E. (1995). Coadministration of nefazodone and benzodiazepines. I. Pharmacodynamic assessment. J. Clin. Psychopharmacol. 15:306-319.
56. Lane, R. M., (1996). Pharmacokinetic drug interaction potential of selective serotonin reuptake inhibitors. Int. Clin. Psychopharmacol. 11:31-61.
57. Langtry, H. D., and Benfield, P. (1990). Zolpidem: A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential. Drugs 40:291-313.
58. Lasher, T. A., Fleishaker, J. C., Steenwyk, R. C., and Antal, E. J. (1991). Pharmacokinetic pharmacodynamic evaluation of the combined administration of alprazolam and fluoxetine. Psychopharmacology 104:323-327.
59. Marks, J. (1985). The Benzodiazepines: Use, Overuse, Misuse, Abuse, 2nd ed., MTP Press, Lancaster, PA.
60. 14C-buspirone HCl after intravenous and oral dosing in man. Clin. Pharmacol. Ther. 37:210 [abstract no. B36].
61. McEvoy, G. K. (ed.) (1989). American Hospital Formulary Service Drug Information, American Society of Hospital Pharmacists, Bethesda, MD.
62. McKenzie, S. G. (1983). Introduction to the pharmacokinetics and pharmacodynamics of benzodiazepines. Prog. Neupsychopharmacol. Biol. Psychiatry 7:623-627.
63. Nebert, D. W., Nelson, D. R., Adesnik, M., Coon, M. J., Estabrook, R. W., Gonzalez, F. J., Guengerich, F. P., Gunsalus, I. C., Johnson, E. F., Kemper. B., Levin, W., Philips, I. R., Sato, R., and Waterman, M. R. (1989). The P450 superfamily: Updated listing of all genes and recommended nomenclature for the chromosomal loci. DNA 8:1-13.
64. Nebert, D. W., Nelson, D. R., Coon, M. J., Estabrook, R. W., Feyereisen, R., Fujii-Kuriyama, Y., Gonzalez, F. J., Guengerich, F. P., Gunsalus, I. C., Johnson, E. F., Loper, J. C., Sato, R., Waterman, M. R., and Waxman, D. J. (1991). The P450 superfamily: Update on new sequences, gene mapping, and recommended nomenclature. DNA Cell Biol. 10:1-14.
65. Nelson, D. R., Koymans, L., Kamataki, T., Stegeman, J. J., Feyereisen, R., Waxman, D. J., Waterman, M. R., Gotoh, O., Coon, J., Estabrook, R. W., Gunsalus, I. C., and Nebert, D. W. (1996). P450 superfamily: Update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 6:1-42.
66. Nemeroff, C. B., DeVane, C. L., and Pollock, B. G. (1996). Newer antidepressants and the cytochrome P450 system. Am. J. Psychiatry 153:311-320.
67. Ochs, H. R., Greenblatt, D. J., Friedman, H., Burnstein, E.S., Locniskar, A., Harmatz, J. S., and Shader, R. I. (1987). Bromazepam pharmacokinetics: Influence of age, gender, oral contraceptives, cimetidine, and propranolol. Clin. Pharmacol. Ther. 41:562-570.
68. Olkkola, K. T., Aranko, K., Luurila, H., Hiller, A., Saarnivaara, L., Himberg, J.-J., and Neuvonen, P. J. (1993). A potentially hazardous interaction between erythromycin and midazolam. Clin. Pharmacol. Ther. 53:298-305.
69. Olkkola, K. T., Backman, J. T., and Neuvonen, P. J., (1994). Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole. Clin. Pharmacol. Ther. 55:481-485.
70. Pichard, L., Gillet, G., Bonfils, C., Domergue, J., Thenot, J. P., and Maurel, P. (1995). Oxidative metabolism of zolpidem by human liver cytochrome P450S. Drug Metab. Disp. 23:1253-1262.
71. Piergies, A. A., Sweet, J., Johnson, M., Roth-Schechter, B. F., and Allard, S. (1996). The effect of coadministration of zolpidem with fluoxetine: Pharmacokinetics and pharmacodynamics. Int. J. Clin. Pharmacol. Ther. 34:178-183.
72. Preskorn, S. H., (1997). Clinically relevant pharmacology of selective serotonin reuptake inhibitors. Clin. Pharmacokinet. 32:1-21.
73. Priest, R. G. (1997). Pharmacological management of insomnia: The current approach. Ther. Express May:1-4.
74. Priest, R. G., Terzano, M. G., Parrino, L., and Boyer, P. (1997). Efficacy of zolpidem in insomnia. Eur. Psychiatry 12 (Suppl. 1):5s-14s.
75. Reidenberg, P., Glue, P., Banfield, C., Colucci, R. D., Meehan, J. W., Radwanski, E., Mojavarian, P., Lin, C. C., Nazamis, J., Guillaume, M., and Affrime, M. (1995). Effects of felbamate on multiple dose pharmacokinetics of phenobarbital. Clin. Pharmacol. Ther. 58:279-287.
76. Richelson, E. (1997). Pharmacokinetic drug interactions of new antidepressants: A review of the effects on the metabolism of other drugs. Mayo Clin. Proc. 72:835-847.
77. Rickels, K. (1985). Benzodiazepines in emotional disorders. In Smith, D. E., and Wesson, D. R. (eds.), The Benzodiazepines: Current Standards for Medical Practice, MTP Press, Lancaster, PA.
78. Rizack, M. A. (ed.) (1995). The Medical Letter Handbook of Adverse Drug Interactions, Medical Letter, New Rochelle, NY.
79. Salvà, P., and Costa, J. (1995). Clinical pharmacokinetics and pharmacodynamics of Zolpidem. Therapeutic implications. Clin. Pharmacokinet. 29:142-153.
80. Salzman, C. (1980). Use of benzodiazepines to control disruptive behavior in inpatients. J. Clin. Psychiatry 49 (Suppl. 12):13-15.
81. Sanders, L. D., Whitehead, C., Gildersleve, C. D., Rosen, M., and Robinson, J. O. (1993). Interaction of H2-receptor antagonists and benzodiazepine sedation. Anaesthesia 48:286-292.
82. Sands, B. F., Creelman, W. L., Ciraulo, D. A., Greenblatt, D. J., andShader, R. I. (1995). Benzodiazepines. In Ciraulo, D. C., Shader, R. I., Greenblatt, D. J., and Creelman, W. L. (eds.), Drug Interactions in Psychiatry, Williams and Wilkins, Baltimore, pp. 214-248.
83. Shaefer, M. S. (1987). The newer benzodiazepines lorazepam and midazolam. Semin. Intervent. Radiol. 4:173-178.
84. Sheehan, D. V. (1987). Benzodiazepines in panic disorder and agoraphobia. J. Affect. Disord. 13:167-181.
85. Smith, D. E., and Wesson, D. R. (1985). Benzodiazepine dependency syndromes. In Smith, D. E., and Wesson, D. R. (eds.), The Benzodiazepines, Current Standards for Medical Practice, MTP Press, Lancaster, PA.
86. Spina, E., Avenoso, A., Campo, G., Caputi, A. P., and Perucca, E. (1994). Phenobarbital induces the CYP2D6-mediated 2-hydroxylation of desipramine. Neuropsychopharmacology 10 (Suppl. 3, Part 2):200S.
87. Taylor, J. L., and Tinklenberg, J. R. (1987). Cognitive impairment and benzodiazepines. In Meltzer, H. Y. (ed.), Psychopharmacology: The Third Generation of Progress, Raven Press, New York.
88. Teboul, E. A., and Chouinard, G. (1990). Principles of benzodiazepine selection. Part I: Pharmacological aspects. Can. J. Psychiatry 35:700-710.
89. Varhe, A., Olkkola, K. T., and Neuvonen, P. J. (1994). Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole or itraconazole. Clin. Pharmacol. Ther. 56:601-607.
90. Venkatakrishnan, K., Greenblatt, D. J., von Moltke, L. L., and Shader, R. I. (1998). Alprazolam is another substrate for human cytochrome P450-3A isoforms. J. Clin. Psychopharmacol. 18:256.
91. Verbeeck, R., Tjandramaga, T. B., Verberckmoes, R., and De Schepper, P. J. (1976). Biotransformation and excretion of lorazepam in patients with chronic renal failure. Br. J. Clin. Pharmacol. 3:1033-1039.
92. von Moltke, L. L., Greenblatt, D. J., Harmatz, J. S., and Shader, R. I. (1993). Alprazolam metabolism in vitro: Studies of human, monkey, mouse and rat liver microsomes. Pharmacology 47:268-276.
93. von Moltke, L. L., Greenblatt, D. J., Court, M. H., Duan, S. X., Harmatz, J. S., and Shader, R. I. (1995). Inhibition of alprazolam and desipramine hydroxylation in vitro by paroxetine and fluvoxamine: Comparison with other selective serotonin reuptake inhibitor antidepressants. J. Clin. Psychopharmacol. 15:125-131.
94. von Moltke, L. L., Greenblatt, D. J., Harmatz, J. S., Duan, S. X., Harrel, L. M., Cotreau-Bibbo, M. M., Pritchard, G. A., Wright, C. E., and Shader, R. (1996a). 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. 276:370-379.
95. von Moltke, L. L., Greenblatt, D. J., Schneider, J., Duan, S. X., Wright, C. E., Harmatz, J. S., and Shader, R. I. (1996b). Midazolam hydroxylation by human liver microsomes in vitro: Inhibition by fluoxetine, norfluoxetine, and by azole antifungal agents. J. Clin. Pharmacol. 36:783-791.
96. Warot, D., Bergougnan, L., Lamiable, D., Berlin, I., Bensimon, G., Danjou, P., and Puech, A. J. (1987). Troleandomycin-triazolam interaction in healthy volunteers: Pharmacokinetic and psychometric evaluation. Eur. J. Clin. Pharmacol. 32:389-393.
97. Weiershausen, U. (1985). Pharmacokinetic considerations in the treatment of chronic anxiety. In Smith, D. E., and Wesson, D. R. (eds.), The Benzodiazepines: Current Standards for Medical Practice, MTP Press, Lancaster, PA.
98. Woods, J. H., Katz, J. L., and Winger, G. (1992). Benzodiazepines: use, abuse and consequences. Pharmacol. Rev. 44:151-347.
99. World Psychiatric Association Task Force Report (1996). Programme on Substance Abuse. Rational Use of Benzodiazepines, World Health Organization, Geneva, Switzerland.