Serum Concentrations of Paliperidone After Administration of the Long-Acting Injectable Formulation

Background: The pharmacokinetics of long-acting intramuscular paliperidone in a naturalistic setting is not well documented. The objective of this study was to investigate the relationship between dose and serum concentrations of paliperidone using data from a routine therapeutic drug monitoring service. Methods: Serum concentration measurements in 310 samples from 110 male and 75 female patients receiving depot injections of paliperidone were retrospectively retrieved from the therapeutic drug monitoring database. Results: The median dose was 100 mg every 28 days. The median concentration/dose (C/D) ratio of paliperidone was 16.1 (nmol/L)/(mg/d), with a 10-90 percentile range of 7.8-31.0 (nmol/L)/(mg/d). Dose-adjusted serum concentrations were 33% higher in patients 65 years or older and more than 50% lower in patients taking the p-glycoprotein inducer carbamazepine. There were no significant effects of sex or dose on the C/D ratio. The median serum concentrations of paliperidone at the end of the dose interval were 31 nmol/L at an intramuscular dose of 50 mg/28 d, 53 nmol/L after a dose of 75 mg/28 d, 59 nmol/L after a dose of 100 mg/28 d, and 93 nmol/L after a dose of 150 mg/28 d. Forty-five percent of the measurements were lower than the suggested therapeutic range of 20-60 ng/mL (47-140 nmol/L). Conclusions: The data show a 4-fold interindividual difference in dose-adjusted serum concentrations within the 10-90 percentile range and illustrate the significant effects of age and p-glycoprotein induction on the pharmacokinetics of paliperidone. The study also indicates that at least in some patients, it might take longer time than anticipated to reach steady state.