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Meng-Na Wang,1,* Hai-Tao Yu,2,* Ya-Qian Li,1 Yun Zeng,1 Shuang Yang,3 Guo-Ping Yang,1,3– 6 Qi Pei,6 Jie Huang1,3 1Center for Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China; 2Research and Development Center, Nanjing Chia Tai Tianqing Pharmaceutical Co., Ltd., Nanjing 210038, People’s Republic of China; 3Research Center of Drug Clinical Evaluation of Central South University, Changsha, Hunan 410013, People’s Republic of China; 4XiangYa School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, People’s Republic of China; 5National-Local Joint Engineering Laboratory of Drug Clinical Evaluation Technology, Changsha, Hunan 410013, People’s Republic of China; 6Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Huang; Qi PeiThe Third Xiangya Hospital, Central South University, Yinpenling Street, Yuelu District, Changsha, Hunan 410013, People’s Republic of ChinaTel +86 15116469024Fax +86 731 8861 8326Email cellahuang1988@163.com; peiqi1028@126.comObjectives: This study was conducted to evaluate the bioequivalence (BE) of a generic form of obeticholic acid (OCA) and OcalivaTM under fasting and fed conditions and to determine the effects of food on the pharmacokinetic (PK) profiles of OCA in healthy Chinese subjects.Methods: A randomized, single-dose, three-sequence, three-period, partial replicated crossover study was conducted with a 21-day washout interval between periods under fasting (n=48) and fed (n=48) conditions. Blood samples for OCA and its metabolites Glyco-OCA and Tauro-OCA were collected up to 168 hours after administration in each period. PK parameters were calculated using the non-compartmental method. Geometric mean ratios for PK parameters of the test to reference drug under fasting and fed conditions and their 90% confidence intervals were estimated. Safety evaluations were carried out all through the study.Results: A total of 91 subjects completed the study with 45 in a fasted state and 46 receiving a high-fat diet. There were no serious or unexpected drug-related adverse events occurring during the study. There was no significant difference in the main PK parameters of the two preparations, irrespective of the fasting or fed conditions. Under fasting and fed conditions, the SWR of lnCmax, lnAUC0-t and lnAUC0-∞ were 0.445, 0.370, 0.448, 0.340, 0.168, and 0.180, respectively. Thus, the average BE or the reference-scaled average BE was used to verify that the two preparations were bioequivalent under fasting and fed conditions. Compared with the fasting state, the AUC0-t of the test drug, the AUC0-t, and AUC0-∞ of the reference drug were higher in the fed state.Conclusion: The test drug and the reference drug were BE and well tolerated in Chinese healthy subjects under both fasting and fed conditions. Food-intake may cause a significant difference in the main PK parameters of the two preparations.Keywords: obeticholic acid, bioequivalence, pharmacokinetics, food effect |
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