Pharmacogenetic and safety analysis of cinacalcet hydrochloride in healthy Chinese subjects
| Autor: | Hongwen Zhang, Yang-Jie Liu, Yi Qian, Xue-Hui Zhang, Lijun Xie, Lu-Ning Sun, Yun Liu, Zeng-Qing Ma, Zi-Ping Cheng, Zi-Qing-Yun Yuan, Yong-Qing Wang, Lei Yu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Cinacalcet business.industry 030232 urology & nephrology Cmax General Medicine 030204 cardiovascular system & hematology Bioequivalence Gastroenterology 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Cinacalcet Hydrochloride Pharmacodynamics Internal medicine medicine Vitamin D and neurology Original Article business Pharmacogenetics medicine.drug |
| Zdroj: | Ann Transl Med |
| ISSN: | 2305-5847 2305-5839 |
| Popis: | BACKGROUND: Our study aims to explore the effect of genetics on the pharmacodynamics (PD) and pharmacokinetics (PK) of cinacalcet in healthy Chinese subjects; to investigate the effect of dietary factors on cinacalcet, and to evaluate the safety of cinacalcet under fasting and non-fasting conditions using a bioequivalence trial. METHODS: We investigated the relationship of cinacalcet PK with single nucleotide polymorphisms (SNPs) of CYP3A4, CYP1A2 and CYP2D6, and of cinacalcet PD with SNPs of calcium-sensitive receptors (CASR) and vitamin D receptors (VDR) in 65 healthy Chinese subjects recruited to participate in this study. Our study was a phase I, open-label, randomized, two-period, two-sequence crossover, a single-center clinical study designed under both fasting and non-fasting conditions to investigate the effect of dietary factors on cinacalcet. Plasma cinacalcet concentrations were analyzed using a validated HPLC-MS/MS assay. Clinical laboratory tests evaluated safety. Thirteen SNPs of CASR, VDR, and CYP genes were selected for pharmacogenetic analysis. RESULTS: CYP3A4 rs4646437 was found to be associated with the PK of cinacalcet under fasting conditions (P |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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