![]() ![]() External validation was only performed in one study to determine the predictive performance of the models. Age, sex, smoking status, and cytochrome P450 1A2 were found to be the most common identified covariates affecting these parameters. Significant interindividual variations of clozapine pharmacokinetic parameters were found in most of the included studies. ![]() Clozapine pharmacokinetics was described as one-compartment with first-order absorption and elimination in most of the studies. Twelve studies were included in this review. Reviews, methodology articles, in vitro and animal studies, and noncompartmental analysis were excluded. A search of publications for population pharmacokinetic analyses of clozapine either in healthy volunteers or patients from inception to April 2019 was conducted in PubMed and SCOPUS databases. Thus, a systematic review was performed (i) to compare published pharmacokinetics models and (ii) to summarize and explore identified covariates influencing the clozapine pharmacokinetics models. Several clozapine population pharmacokinetic models have been introduced in the last decades. ![]() Clozapine is a second-generation antipsychotic drug that is considered the most effective treatment for refractory schizophrenia. ![]()
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