Clinical pharmacology study of cariprazine (MP-214) in patients with schizophrenia (12-week treatment)
| Autor: | Tadakatsu Nakamura, Atsushi Iwakaji, Masayoshi Imada, Tomoko Kubota, Yasunori Morio, Margit Kapás |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male cariprazine didesmethyl-cariprazine Pharmaceutical Science Cariprazine Pharmacology behavioral disciplines and activities Partial agonist Piperazines law.invention 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics law Dopamine Dopamine receptor D2 mental disorders Drug Discovery medicine Humans Original Research Clinical pharmacology Drug Design Development and Therapy Dose-Response Relationship Drug desmethyl-cariprazine business.industry Desmethyl Middle Aged medicine.disease 030227 psychiatry schizophrenia Treatment Outcome chemistry Schizophrenia Female business pharmacokinetics 030217 neurology & neurosurgery medicine.drug Antipsychotic Agents Follow-Up Studies Half-Life |
| Zdroj: | Drug Design, Development and Therapy |
| ISSN: | 1177-8881 |
| Popis: | Tadakatsu Nakamura,1 Tomoko Kubota,1 Atsushi Iwakaji,1 Masayoshi Imada,1 Margit Kapás,2 Yasunori Morio1 1Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan; 2Developmental Drug Metabolism and Pharmacokinetics, Gedeon Richter Plc, Budapest, Hungary Purpose: Cariprazine is a potent dopamine D3-preferring D3/D2 receptor partial agonist in development for the treatment of schizophrenia, bipolar mania, and depression. Pharmacokinetics of cariprazine and the two clinically relevant metabolites (desmethyl- and didesmethyl-cariprazine) was evaluated in a clinical pharmacology study. Methods: This was a multicenter, randomized, open-label, parallel-group, fixed-dose (3, 6, or 9mg/day) study of 28-week duration (≤4-week observation, 12-week open-label treatment, and 12-week follow-up). Once-daily cariprazine was administered to 38 adult patients with schizophrenia. The pharmacokinetics of cariprazine, metabolites, and total active moieties (sum of cariprazine and two metabolites) was evaluated; efficacy and safety were also assessed. Results: Steady state was reached within 1–2weeks for cariprazine and desmethyl-cariprazine, 4weeks for didesmethyl-cariprazine, and 3weeks for total active moieties. Cariprazine and desmethyl-cariprazine levels decreased >90% within 1week after the last dose, didesmethyl-cariprazine decreased ~50% at 1week, and total active moieties decreased ~90% within 4weeks. Terminal half-lives of cariprazine, desmethyl-cariprazine, and didesmethyl-cariprazine ranged from 31.6 to 68.4, 29.7 to 37.5, and 314 to 446hours, respectively. Effective half-life (calculated from time to steady state) of total active moieties was ~1week. Incidence of treatment-emergent adverse events was 97.4%; 15.8% of patients discontinued due to adverse events. Noabnormal laboratory values or major differences from baseline in extrapyramidal symptoms were observed. Conclusion: Cariprazine and its active metabolites reached steady state within 4weeks, and exposure was dose proportional over the range of 3–9mg/day. Once-daily cariprazine was generally well tolerated in adult patients with schizophrenia. Keywords: schizophrenia, cariprazine, pharmacokinetics, desmethyl-cariprazine, didesmethyl-cariprazine |
| Databáze: | OpenAIRE |
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