Olanzapine: Interaction study with imipramine

John Callaghan, Benito J. Cerimele, Kelem J. Kassahun, Eldon H. Nyhart, Pamela J. Hoyes-Beehler, George V. Kondraske

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Olanzapine is an 'atypical' antipsychotic agent with a high affinity for serotonin 5HT(2A/C), 5HT 3, 5HT 6, and dopamine D 1, D 2, D 3, D 4 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.

Original languageEnglish
Pages (from-to)971-978
Number of pages8
JournalJournal of Clinical Pharmacology
Volume37
Issue number10
StatePublished - Oct 1997

Fingerprint

olanzapine
Imipramine
Cytochrome P-450 CYP2D6
Desipramine
Vital Signs
Pharmacokinetics
Drug Interactions
Antipsychotic Agents
Psychomotor Performance
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP1A2
Orthostatic Hypotension
Psychotic Disorders
Cross-Over Studies
Antidepressive Agents
Fingers
Dopamine
Serotonin

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Callaghan, J., Cerimele, B. J., Kassahun, K. J., Nyhart, E. H., Hoyes-Beehler, P. J., & Kondraske, G. V. (1997). Olanzapine: Interaction study with imipramine. Journal of Clinical Pharmacology, 37(10), 971-978.

Olanzapine : Interaction study with imipramine. / Callaghan, John; Cerimele, Benito J.; Kassahun, Kelem J.; Nyhart, Eldon H.; Hoyes-Beehler, Pamela J.; Kondraske, George V.

In: Journal of Clinical Pharmacology, Vol. 37, No. 10, 10.1997, p. 971-978.

Research output: Contribution to journalArticle

Callaghan, J, Cerimele, BJ, Kassahun, KJ, Nyhart, EH, Hoyes-Beehler, PJ & Kondraske, GV 1997, 'Olanzapine: Interaction study with imipramine', Journal of Clinical Pharmacology, vol. 37, no. 10, pp. 971-978.
Callaghan J, Cerimele BJ, Kassahun KJ, Nyhart EH, Hoyes-Beehler PJ, Kondraske GV. Olanzapine: Interaction study with imipramine. Journal of Clinical Pharmacology. 1997 Oct;37(10):971-978.
Callaghan, John ; Cerimele, Benito J. ; Kassahun, Kelem J. ; Nyhart, Eldon H. ; Hoyes-Beehler, Pamela J. ; Kondraske, George V. / Olanzapine : Interaction study with imipramine. In: Journal of Clinical Pharmacology. 1997 ; Vol. 37, No. 10. pp. 971-978.
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