The Elimination Rate after Clozapine Overdose in Chinese Schizophrenia Patients: A Population Pharmacokinetics Model Study

Abstract

Introduction: The prescribing of clozapine in China is common because of its outstanding efficacy and low price. There have been many cases of clozapine overdose in China. However, studies about the pharmacokinetics after overdose in the Chinese have rarely been reported. Population pharmacokinetics (PopPK) can analyze sparse data, and it is appropriate to compute clozapine pharmacokinetics after overdose.

Methods: There were 47 clozapine overdose cases. We constructed a single-compartment first-order elimination PopPK model. We also considered some covariates that can influence the pharmacokinetics parameters.

Results: 21 cases were included in the analysis. When the reported toxic dosage was 3 740 mg, the elimination rate constant of the population was 0.0258(h⁻¹). The elimination half-life was 26.9 h. The coefficient of random variation was 17%.

Discussion: PopPK can solve the problem of sparse data after overdose. The area under the concentration-time curve after clozapine overdose exhibited the “two peaks phenomenon.” The reported toxic dosage could impact clozapine elimination after overdose. Delayed absorption of clozapine is the best explanation for this finding.

Key words

clozapine - overdose - population pharmacokinetics - suicide

^* These authors contributed equally to this paper.

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