RT Journal Article
SR Electronic
T1 Apixaban and Rosuvas­­tatin Pharmacokinetics in Nonalcoholic Fatty Liver Disease
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 485
OP 492
DO 10.1124/dmd.117.079624
VO 46
IS 5
A1 Tirona, Rommel G.
A1 Kassam, Zahra
A1 Strapp, Ruth
A1 Ramu, Mala
A1 Zhu, Catherine
A1 Liu, Melissa
A1 Schwarz, Ute I.
A1 Kim, Richard B.
A1 Al-Judaibi, Bandar
A1 Beaton, Melanie D.
YR 2018
UL http://dmd.aspetjournals.org/content/46/5/485.abstract
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 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 of apixaban or rosuvastatin.