PT - JOURNAL ARTICLE AU - Rommel G. Tirona AU - Zahra Kassam AU - Ruth Strapp AU - Mala Ramu AU - Catherine Zhu AU - Melissa Liu AU - Ute I. Schwarz AU - Richard B. Kim AU - Bandar Al-Judaibi AU - Melanie D Beaton TI - Apixaban and Rosuvastatin Pharmacokinetics in Nonalcoholic Fatty Liver Disease AID - 10.1124/dmd.117.079624 DP - 2018 Jan 01 TA - Drug Metabolism and Disposition PG - dmd.117.079624 4099 - http://dmd.aspetjournals.org/content/early/2018/02/22/dmd.117.079624.short 4100 - http://dmd.aspetjournals.org/content/early/2018/02/22/dmd.117.079624.full AB - 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 (N=22) and healthy controls (N=12). The areas under the plasma concentration-time curve (AUC0-12) for apixaban were not different between control and NAFLD subjects (671 and 545 ng/mL×hr, respectively; P=0.15). In multivariable linear regression analyses, only participant weight but not NAFLD, age or SLCO1B1/ABCG2/CYP3A5 genotypes, was associated with apixaban and rosuvastatin AUC0-12 (P<0.001 and P=0.06). Similarly, the AUC0-12 for rosuvastatin did not differ between control and NAFLD groups (25.4 and 20.1 ng/mL×hr, respectively; P=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 (P<0.001 and P<0.05, respectively). NAFLD does not appear to affect the pharmacokinetics of apixaban or rosuvastatin.