Ketoconazole inhibition of triazolam and alprazolam clearance: Differential kinetic and dynamic consequences

Kinetic and dynamic consequences of metabolic inhibition were evaluated in a study of the interaction of ketoconazole, a P4503A inhibitor, with alprazolam and triazolam, two 3A substrate drugs with different kinetic profiles.

[1]  D. Greenblatt,et al.  Population study of triazolam pharmacokinetics. , 1986, British journal of clinical pharmacology.

[2]  D. Greenblatt,et al.  Effects of ketoconazole on triazolam pharmacokinetics, pharmacodynamics and benzodiazepine receptor binding in mice. , 1998, The Journal of pharmacology and experimental therapeutics.

[3]  G. Kaplan,et al.  Dose‐Dependent Pharmacokinetics and Psychomotor Effects of Caffeine in Humans , 1997, Journal of clinical pharmacology.

[4]  D. Greenblatt,et al.  Sedative effects and impaired learning and recall after single oral doses of lorazepam , 1986, Clinical pharmacology and therapeutics.

[5]  P. Neuvonen,et al.  Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole or itraconazole , 1994, Clinical pharmacology and therapeutics.

[6]  D. Greenblatt,et al.  Inhibitors of alprazolam metabolism in vitro: effect of serotonin-reuptake-inhibitor antidepressants, ketoconazole and quinidine. , 1994, British journal of clinical pharmacology.

[7]  David W. Warnock,et al.  Clinical Pharmacokinetics of Ketoconazole , 1988, Clinical pharmacokinetics.

[8]  D J Greenblatt,et al.  Pharmacokinetic-Pharmacodynamic Relationships For Benzodiazepines , 1996, Clinical pharmacokinetics.

[9]  D. Greenblatt,et al.  Metabolism of Drugs by Cytochrome P450 3A Isoforms , 1995, Clinical pharmacokinetics.

[10]  D. Greenblatt,et al.  Inhibition of Human Cytochrome P450‐3A Isoforms by Fluoxetine and Norfluoxetine: In Vitro and In Vivo Studies , 1996, Journal of clinical pharmacology.

[11]  T. Kronbach,et al.  Oxidation of midazolam and triazolam by human liver cytochrome P450IIIA4. , 1989, Molecular pharmacology.

[12]  S. Pond,et al.  First-Pass Elimination Basic Concepts and Clinical Consequences , 1984, Clinical pharmacokinetics.

[13]  J. V. Etzel Oral azole drugs as systemic antifungal therapy. , 1994, The New England journal of medicine.

[14]  D. Greenblatt,et al.  Electron-capture gas chromatographic analysis of the triazolobenzodiazepines alprazolam and triazolam. , 1981, Journal of chromatography.

[15]  D. Greenblatt Presystemic Extraction: Mechanisms and Consequences , 1993, Journal of clinical pharmacology.

[16]  J S Harmatz,et al.  Triazolam biotransformation by human liver microsomes in vitro: effects of metabolic inhibitors and clinical confirmation of a predicted interaction with ketoconazole. , 1996, The Journal of pharmacology and experimental therapeutics.

[17]  D. Greenblatt,et al.  Sensitivity to triazolam in the elderly. , 1991, The New England journal of medicine.

[18]  D. Greenblatt,et al.  Relationship of in vitro data on drug metabolism to in vivo pharmacokinetics and drug interactions: implications for diazepam disposition in humans. , 1996, Journal of clinical psychopharmacology.

[19]  J S Harmatz,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. , 1994, The Journal of pharmacology and experimental therapeutics.

[20]  Grant R. Wilkinson,et al.  A physiological approach to hepatic drug clearance , 1975 .

[21]  G. Granneman,et al.  Use of In Vitro and In Vivo Data to Estimate the Likelihood of Metabolic Pharmacokinetic Interactions , 1997, Clinical pharmacokinetics.

[22]  M. Danhof,et al.  Electroencephalogram Effect Measures and Relationships Between Pharmacokinetics and Pharmacodynamics of Centrally Acting Drugs , 1992, Clinical pharmacokinetics.

[23]  P. Kroboth,et al.  Triazolam pharmacokinetics after intravenous, oral, and sublingual administration. , 1995, Journal of clinical psychopharmacology.

[24]  S. Cox,et al.  Effect of ranitidine on the disposition of orally and intravenously administered triazolam. , 1991, Clinical pharmacy.

[25]  G R Wilkinson,et al.  Clearance approaches in pharmacology. , 1987, Pharmacological reviews.

[26]  D. Greenblatt,et al.  Kinetic and dynamic study of intravenous lorazepam: comparison with intravenous diazepam. , 1989, The Journal of pharmacology and experimental therapeutics.

[27]  D. Greenblatt,et al.  The clinician and drug interactions--an update. , 1996, Journal of clinical psychopharmacology.

[28]  D. Greenblatt,et al.  The importance of presystemic extraction in clinical psychopharmacology. , 1996, Journal of clinical psychopharmacology.

[29]  C. Battel Pharmacokinetic and electroencephalographic study of intravenous diazepam, midazolam, and placebo , 1989 .

[30]  D. Greenblatt,et al.  In vitro approaches to predicting drug interactions in vivo. , 1998, Biochemical pharmacology.

[31]  D. Greenblatt,et al.  Gas chromatographic analysis of alprazolam in plasma: replicability, stability and specificity. , 1990, Journal of chromatography.

[32]  D. Greenblatt,et al.  Distinguishing a benzodiazepine agonist (triazolam) from a nonagonist anxiolytic (buspirone) by electroencephalography: Kinetic‐dynamic studies , 1994, Clinical pharmacology and therapeutics.