Defining the therapeutic reference range for cariprazine

Introduction According to the Consensus Guideline, “therapeutic reference range” (TRR) defines ranges of drug blood concentrations that specify a lower limit below which drug-induced therapeutic response is unlikely occur and an upper above tolerability decreases or improvement ceases. The TRR can be obtained from concentration measurements (trough (pre-dose) plasma under steady-state conditions) in studies at therapeutically effective doses. Objectives aim examine for cariprazine (CAR: 1.5 mg/day 6 mg/day) schizophrenia studies. Methods population based CAR derived by PK/PD evaluation phase 2/3 efficacy with sparse PK sampling. simulated compared actually measured values two As active metabolites also contribute effect, exposure given Total (CAR + DCAR DDCAR) parent (CAR). Results analyses demonstrated increase increasing exposure. These results are related trough ca. 30 nM 100 determine limits. For drug, pre-dose mean was between 5.7-10 ng/mL different studies, while it 1.9 ng/mL. Conclusions levels steady state – 2-10 (unchanged drug) treatment. Disclosure Interest M. Kapás Employee of: Gedeon Richter Plc., A. Horváth D. Djuric R. Csehi Á. Barabássy Plc.