Population pharmacokinetics of blonanserin in Japanese adolescent and adult patients with schizophrenia.

Abstract

The second-generation antipsychotic blonanserin is a highly selective, full antagonist of dopamine D₂ and D₃ and serotonin 5-HT_2A receptors. It is currently prescribed for patients with schizophrenia in Japan. We aimed to develop a population pharmacokinetic model of oral blonanserin, including data from 12 to 77 years old patients, to assess the covariates that influence blonanserin pharmacokinetics and evaluate appropriate dosage regimens in adolescents versus adults. The population pharmacokinetic analysis was conducted using plasma concentrations in 132 Japanese adolescent and 135 adult patients with schizophrenia (including 20 older adults [≥65 years] patients), and 49 healthy adults. The blonanserin population pharmacokinetics was described using a two-compartment model with first-order absorption with lag time. Relative bioavailability decreased in fasted conditions and with concomitant CYP3A4 inducer use. Apparent clearance in older adult was lower than adult and adolescent. Simulation revealed similar plasma exposures between adolescents and adults and slightly larger in older adults. Bayesian estimates of apparent clearance suggested no effects of age in adolescents between 12 and 18 years old. Together, these results reveal the pharmacokinetic characteristics of blonanserin over a wide age range and support the appropriateness of the approved dosing regimen for adolescent patients with schizophrenia in Japan.