Therapeutic Drug Monitoring of Olanzapine and Cytochrome P450 Genotyping in Nonsmoking Subjects

• Published in: Therapeutic drug monitoring Vol. 42; no. 2; p. 325
• Main Authors: Miroshnichenko, Igor I, Pozhidaev, Ivan V, Ivanova, Svetlana A, Baymeeva, Natalia V
• Format: Journal Article
• Language: English
• Published: United States 01.04.2020
• Subjects: Adult; Antipsychotic Agents - pharmacokinetics; Antipsychotic Agents - therapeutic use; Chromatography, Liquid; Cytochrome P-450 CYP2D6 - genetics; Cytochrome P-450 CYP2D6 - metabolism; Drug Monitoring - methods; Genotype; Humans; Male; Non-Smokers; Olanzapine - pharmacokinetics; Olanzapine - therapeutic use; Prospective Studies; Psychotic Disorders - drug therapy; Real-Time Polymerase Chain Reaction; Schizophrenia - drug therapy; Tandem Mass Spectrometry; Young Adult
• ISSN: 1536-3694
• DOI: 10.1097/FTD.0000000000000695

The relationship between a daily dose of olanzapine, its serum concentration, and the genotype of young nonsmoking men treated for schizophrenia or schizophreniform disorder was investigated in day-to-day clinical practice. Pharmacogenetics was also examined for the selected patients. A total of 49 participants were recruited as in-patients at the Mental Health Research Center (Moscow, Russia). Inclusion criteria were patients who had been diagnosed with schizophrenia or schizoaffective disorder (following DSM-IV guidelines) and were being treated with OLZ. A prospective, observational, open-study design was implemented. In line with the literature, patients were only included if they attained steady-state OLZ concentrations lasting for at least 8 days. A liquid chromatographic-tandem mass spectrometric method was developed for analyzing OLZ in human serum. The single cytochrome P450 polymorphisms were genotyped using an amplifier real-time polymerase chain reaction system following standard protocols. Evidence indicating that CYP2D6 polymorphism has a significant (P = 0.046) effect on the pharmacokinetics of olanzapine was obtained, confirming the beneficial effects of therapeutic drug monitoring (TDM) for olanzapine. TDM should therefore be used as a standard care during olanzapine therapy. TDM is also useful in assessing adherence and may have a role in limiting olanzapine dosage geared at minimizing the risk of long-term toxicity.