Olanzapine: Interaction Study with Imipramine

Olanzapine is an “atypical” antipsychotic agent with a high affinity for serotonin 5HT2A/C, 5HT3, 5HT6, and dopamine D1, D2, D3, D4 receptors. Depressed patients with psychotic disorders frequently require treatment with concomitant antipsychotic and antidepressant medications. Imipramine pharmacoki...

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Bibliographic Details
Published in:	Journal of clinical pharmacology Vol. 37; no. 10; pp. 971 - 978
Main Authors:	Callaghan, John T., Cerimele, Benito J., Kassahun, Kelem J., Nyhart Jr, Eldon H., Hoyes-Beehler, Pamela J., Kondraske, George V.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-10-1997 Sage Science
Subjects:	Adrenergic Uptake Inhibitors - adverse effects Adrenergic Uptake Inhibitors - blood Adrenergic Uptake Inhibitors - pharmacology Adult Analysis of Variance Antipsychotic Agents - adverse effects Antipsychotic Agents - blood Antipsychotic Agents - pharmacology Benzodiazepines Biological and medical sciences Cross-Over Studies Drug Interactions Humans Hypotension, Orthostatic - blood Imipramine - adverse effects Imipramine - blood Imipramine - pharmacology Male Medical sciences Middle Aged Neuropharmacology Olanzapine Pharmacology. Drug treatments Pirenzepine - adverse effects Pirenzepine - analogs & derivatives Pirenzepine - blood Pirenzepine - pharmacology Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychomotor Performance - drug effects Psychopharmacology Single-Blind Method Human Drug combination Unspecific monooxygenase Olanzapine Enzyme Isozyme Psychotropic Toxicity Cytochrome P450 Liver Tricyclic compound Metabolism Crossover study Imipramine Randomization Secondary effect Antidepressant agent Drug-metabolizing enzyme Drug interaction Oxidoreductases Pharmacokinetics
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Summary:	Olanzapine is an “atypical” antipsychotic agent with a high affinity for serotonin 5HT2A/C, 5HT3, 5HT6, and dopamine D1, D2, D3, D4 receptors. Depressed patients with psychotic disorders frequently require treatment with concomitant antipsychotic and antidepressant medications. Imipramine pharmacokinetics serve as a marker for hepatic CYP2D6, CYP1A2, CYP3A activity. An open‐label, three‐way randomized crossover study was done to determine the safety, pharmacokinetics, and potential for a drug interaction between olanzapine (5 mg) and imipramine (75 mg). Each drug was administered alone and in combination. Nine healthy men, ages 32 to 54 years, enrolled in the study. Psychomotor performance capacities, plasma olanzapine, imipramine, desipramine concentrations, and clinical laboratory tests were measured. Pharmacokinetic variables, vital signs, subjective tests for liveliness, and psychomotor outcomes were analyzed using a two‐way ANOVA. Olanzapine was safe. Sedation, postural hypotension, and minor vital sign alterations occurred during all treatments. On the liveliness questionnaire, patients generally reported poorer (less lively) scores with olanzapine alone or coadministered with imipramine versus baseline scores. These effects disappeared within 24 hours after administration. Olanzapine alone and in combination decreased motor‐speed tasks (finger tapping and visual‐arm random reach) compared with baseline or imipramine treatment. Peak 6‐hour changes were statistically significant but clinical importance was only marginal. Olanzapine concentrations were <19% greater than with imipramine. But olanzapine did not affect the kinetics of imipramine or desipramine and, therefore, did not show a metabolic drug interaction involving CYP2D6. J Clin Pharmacol 1997;37:971–978.
Bibliography:	istex:2A2B5656C72FAB9E76296CE4D4CF642E5C6215F7 ArticleID:JCPH4272 ark:/67375/WNG-2QG38TLF-V
ISSN:	0091-2700 1552-4604
DOI:	10.1002/j.1552-4604.1997.tb04272.x