ArticleCNS drugs2024
Semi-physiological Pharmacokinetic Model of Clozapine and Norclozapine in Healthy, Non-smoking Volunteers: The Impact of Race and Genetics.
Article in CNS drugs, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07262736 (Pharmacokinetics of Clozapine and Norclozapine and the Effect of Pantoprazole), which is not on this map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pharmacokinetics of Clozapine and Norclozapine and the Effect of Pantoprazole
Who cites it
3 citing papers in PubMed.
- The Impact of Fluvoxamine on Clozapine and Norclozapine Serum Concentrations.European journal of drug metabolism and pharmacokinetics · 2026Article
- Machine Learning Models for Predicting Antipsychotic Effectiveness and Separate Cost-Effectiveness Analysis in Hospitalized Schizophrenia Patients.Neuropsychiatric disease and treatment · 2026Article
- Pharmacogenetics and pharmacometabolomics predictors of clozapine and norclozapine pharmacokinetic exposure in healthy volunteers.European journal of clinical pharmacology · 2025Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
BACKGROUND AND
objectivesClozapine is the medication of choice for treatment-resistant schizophrenia. However, it has a complex metabolism and unexplained interindividual variability. The current work aims to develop a pharmacokinetic model of clozapine and norclozapine in non-smokers and assess the impact of demographic and genetic predictors.
methodsHealthy volunteers were recruited in a population pharmacokinetic study. Blood samples were collected at 30 min and 1, 2, 3, 5 and 8 h following a single flat dose of clozapine (12.5 mg). The clozapine and norclozapine concentrations were measured via high-performance liquid chromatography-ultraviolet method. A semi-physiological pharmacokinetic model of clozapine and norclozapine was developed using nonlinear mixed-effects modeling. Clinical and genetic predictors were evaluated, including CYP1A2 (rs762551) and ABCB1 (rs2032582), using restriction fragment length polymorphism.
resultsA total of 270 samples were collected from 33 participants. The data were best described using a two-compartment model for clozapine and a two-compartment model for norclozapine with first-order absorption and elimination and pre-systemic metabolism. The estimated (relative standard error) clearance of clozapine and norclozapine were 27 L h
conclusionsThis is the first study to develop a semi-physiological pharmacokinetic model of clozapine and norclozapine accounting for the pre-systemic metabolism. Asians required lower doses of clozapine as compared with Caucasians, while clozapine pharmacokinetics in sub-Saharan Africans should be further investigated in larger trials.
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Registered trials
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