Abstract
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.
- clinical pharmacology
- human/clinical
- liver disease
- pharmacokinetics
- Transporter-mediated drug/metabolite disposition
- The American Society for Pharmacology and Experimental Therapeutics