Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10162004 | Journal of Pharmaceutical Sciences | 2015 | 9 Pages |
Abstract
The combined clearance of endogenous 6β-hydroxycortisol and 6β-hydroxycortisone is suggested biomarker for in vivo cytochrome P450 3A (CYP3A) activity. We aimed to determine whether the combined clearance of these two markers together with information of biopharmaceutics classification system (BCS) of drugs could be used to predict CYP3A-mediated metabolism of immunosuppressants. The BCS of drug formulations were determined based on the solubility and permeability. Sixty-seven healthy subjects were divided into three groups and group 1 (n = 23), 2 (n = 22), and 3 (n = 22) received oral single dose of cyclosporine, tacrolimus, and sirolimus, respectively. Blood and urine samples were gathered at various times. The combined clearance of 6β-hydroxycortisol and 6β-hydroxycortisone correlated significantly with cyclosporine pharmacokinetics (p < 0.001) after oral dose of a BCS 1 formulation, whereas no relationships were seen after administration of tacrolimus and sirolimus formulations, both of which belonged to BCS 2. Regarding the biopharmaceutical characteristics, the endogenous CYP3A biomarker explains 74.5% of variability in oral cyclosporine clearance between individuals. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3578-3586, 2015
Keywords
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Xi Luo, Liyun Zheng, Ningfang Cai, Qing Liu, Shuang Yang, Xiaoai He, Zeneng Cheng,