Apixaban and Rosuvas--tatin Pharmacokinetics in Nonalcoholic Fatty Liver Disease

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Rommel G TironaMelanie D Beaton

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 control subjects (N = 12). The area under the concentration-time curve to the last sampling time (AUC0-12) values for apixaban were not different between control and NAFLD subjects (671 and 545 ng/ml × hour, respectively; P = 0.15). Similarly, the AUC0-12 values for rosuvastatin did not differ between the control and NAFLD groups (25.4 and 20.1 ng/ml × hour, 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). 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, respectively). NAFLD does not appear to affect the pharmacokinetics...Continue Reading

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Citations

Oct 21, 2019·Clinical Pharmacology and Therapeutics·Anna VildhedeManthena V S Varma
May 16, 2019·Clinical Pharmacokinetics·Wonkyung ByonCharles E Frost
Oct 20, 2020·Internal and Emergency Medicine·Francesco VioliDaniele Pastori
Sep 9, 2020·Clinical Pharmacology and Therapeutics·Noora SjöstedtKim L R Brouwer

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