Title: Quantifying intraindividual variations in plasma clozapine levels: a population pharmacokinetic approach
year: 2016
Journal: J Clin Psychiatry
Volume: 77
Issue: 5
Pages: 681-7
Epubdate: 03/05/2016
date: May
Alternate Journal: The Journal of clinical psychiatry
ISSN: 0160-6689
Article Number: 27136679
Abstract: OBJECTIVE: Clozapine has strong recommendations for therapeutic drug monitoring. While factors that influence interindividual variation in plasma clozapine levels have been extensively reported, intraindividual variation remains poorly studied. We employed a population pharmacokinetic approach to assess intraindividual variations in plasma levels of both clozapine and N-desmethylclozapine, as well as the impact of smoking on this variability. METHODS: Patients who were initiated on clozapine from January 2009 to December 2010 and who provided at least 2 plasma samples were included in this study. The observed concentrations of clozapine and N-desmethylclozapine were applied in a Bayesian pharmacokinetic modeling approach by using a previously published pharmacokinetic model from an independent sample to compute a predicted concentration. The predicted concentrations of clozapine and N-desmethylclozapine were then compared with the observed concentrations in the form of a ratio: predicted-to-observed concentration ratio (Cpred/Cobs). The coefficient of variation of the Cpred/Cobs ratios was taken as a measure of intraindividual variation. RESULTS: A total of 723 plasma levels from 61 patients were included in this analysis. The coefficient of variation of Cpred/Cobs ratios for clozapine and N-desmethylclozapine were 29.8% (SD = 17.2%) and 27.4% (SD = 16.4%), respectively. Though values were higher, smoking did not have a significant effect on coefficients of variation of clozapine (33.5% vs 26.3%, P = .184) or N-desmethylclozapine (30.7% vs 24.2%, P = .100). CONCLUSIONS: Clinicians need to be aware of intraindividual variability and not assume that plasma levels are static. If plasma levels are used to guide dosing of clozapine, serial measurements rather than a single level might be necessary to make an informed clinical decision. The clinical implications of intraindividual variability in plasma clozapine levels need further study.
Notes: 1555-2101 Lee, Jimmy Bies, Robert Takeuchi, Hiroyoshi Fervaha, Gagan Bhaloo, Amaal Powell, Valerie Remington, Gary Journal Article United States J Clin Psychiatry. 2016 May;77(5):681-7. doi: 10.4088/JCP.14m09714.
URI: https://open-access.imh.com.sg/handle/123456789/5051
Authors Address: Schizophrenia Division, Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario M5T 1R8, Canada jimmy_lee@imh.com.sg.
Database Provider: NLM
language: eng
Appears in Collections:2016

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