Characterization of Population Pharmacokinetics of Cariprazine and Its Major Metabolites

Conference: American Psychiatric Association (APA)
Division: Cognigen


Background: Population pharmacokinetic (PK) analysis was undertaken to describe the concentration‑time profiles of cariprazine and its 2 major metabolites of similar pharmacological activity, desmethyl‑cariprazine (DCAR) and didesmethyl‑cariprazine (DDCAR), and to assess the potential impact of demographic covariates, creatinine clearance, and metabolizer status.

Methods: Data were obtained from 3 Phase 1 and 10 Phase 2/3 studies in adult patients (18–65 y) with schizophrenia or bipolar mania. The combined dataset consisted of 13,227 cariprazine, 12,462 DCAR, and 12,092 DDCAR samples from 2199, 2180, and 2140 patients, respectively. Patients (66% male; mean weight 79 kg; mean age 39 y) were administered once‑daily doses of 0.5–12.5 mg (various titrations). In 4 studies, serial sampling was performed over 24 hours following the first dose, and over 24, 168, or 2016 hours following the final dose (depending on study). In remaining studies, 4–9 non‑serial blood samples were drawn at various times during the studies. Population PK modeling was performed using NONMEM, a nonlinear mixed‑effects modeling software package. Compartmental modeling was performed sequentially, wherein the elimination rate of cariprazine served as the formation rate of DCAR, and the elimination rate of DCAR, with a delay, served as the formation rate for DDCAR. Standard pharmacometric practices for population model development and evaluation of covariates were utilized.

169th Annual Meeting of the American Psychiatric Association (APA). May 14-18, 2016, Atlanta, Georgia

By Antonia Periclou, PhD, Luann Phillips, MS, Sébastien Bihorel, PharmD, PhD, Parviz Ghahramani, PhD, Margit Kapás, PhD, Timothy Carrothers, ScD, Tatiana Khariton, PhD