Department of Physiology and Pharmacology (R.G.T., C.Z., U.I.S, R.B.K.), Division of Clinical Pharmacology, Department of Medicine (R.G.T., C.Z., M.L., U.I.S., R.B.K.), Department of Medical Imaging (Z.K.), Division of Gastroenterology, Department of Medicine (B.A.-J., M.D.B.), and Lawson Health Research Institute (R.G.T., Z.K., R.S., M.R., U.I.S., R.B.K., M.D.B.), University of Western Ontario, London, Ontario, Canada; and Department of Medicine, University of Rochester, Rochester, New York (B.A.-J.).
Department of Physiology and Pharmacology (R.G.T., C.Z., U.I.S, R.B.K.), Division of Clinical Pharmacology, Department of Medicine (R.G.T., C.Z., M.L., U.I.S., R.B.K.), Department of Medical Imaging (Z.K.), Division of Gastroenterology, Department of Medicine (B.A.-J., M.D.B.), and Lawson Health Research Institute (R.G.T., Z.K., R.S., M.R., U.I.S., R.B.K., M.D.B.), University of Western Ontario, London, Ontario, Canada; and Department of Medicine, University of Rochester, Rochester, New York (B.A.-J.)
Drug Metab Dispos. 2018 May;46(5):485-492. doi: 10.1124/dmd.117.079624. Epub 2018 Feb 22.
There is little known about the impact of nonalcoholic fatty liver disease (NAFLD) on drug metabolism and transport. We examined the pharmacokinetics of oral apixaban (2.5 mg) and rosuvastatin (5 mg) when administered simultaneously in subjects with magnetic resonance imaging-confirmed NAFLD ( = 22) and healthy control subjects ( = 12). The area under the concentration-time curve to the last sampling time (AUC) values for apixaban were not different between control and NAFLD subjects (671 and 545 ng/ml × hour, respectively; = 0.15). Similarly, the AUC values for rosuvastatin did not differ between the control and NAFLD groups (25.4 and 20.1 ng/ml × hour, respectively; = 0.28). Furthermore, hepatic fibrosis in NAFLD subjects was not associated with differences in apixaban or rosuvastatin pharmacokinetics. Decreased systemic exposures for both apixaban and rosuvastatin were associated with increased body weight ( < 0.001 and < 0.05, respectively). In multivariable linear regression analyses, only participant weight but not NAFLD, age, or // genotypes, was associated with apixaban and rosuvastatin AUC ( < 0.001 and = 0.06, respectively). NAFLD does not appear to affect the pharmacokinetics of apixaban or rosuvastatin.
关于非酒精性脂肪性肝病 (NAFLD) 对药物代谢和转运的影响知之甚少。我们在经磁共振成像证实患有 NAFLD 的受试者（n = 22）和健康对照受试者（n = 12）中同时给予口服阿哌沙班（2.5 mg）和瑞舒伐他汀（5 mg），研究了这两种药物的药代动力学。阿哌沙班的浓度-时间曲线下至最后采样时间的面积（AUC）值在对照组和 NAFLD 组之间没有差异（分别为 671 和 545 ng/ml × 小时； = 0.15）。同样，瑞舒伐他汀的 AUC 值在对照组和 NAFLD 组之间也没有差异（分别为 25.4 和 20.1 ng/ml × 小时； = 0.28）。此外，NAFLD 受试者的肝纤维化与阿哌沙班或瑞舒伐他汀的药代动力学无差异。阿哌沙班和瑞舒伐他汀的全身暴露量减少与体重增加有关（<0.001 和 <0.05，分别）。在多变量线性回归分析中，只有受试者体重，而不是 NAFLD、年龄或 // 基因型，与阿哌沙班和瑞舒伐他汀的 AUC 相关（<0.001 和 = 0.06，分别）。NAFLD 似乎不会影响阿哌沙班或瑞舒伐他汀的药代动力学。
