Apixaban is metabolized by cytochrome P450 (CYP) 3A4 in the liver and intestine, undergoes direct intestinal excretion, and is a substrate to permeability glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters. We examined the drug interactions between cyclosporine and tacrolimus (combined inhibitors of CYP3A4, P-gp and, BCRP) with apixaban in 12 healthy adult male volunteers. Apixaban 10 mg was administered orally alone, in combination with 100 mg cyclosporine or 5 mg tacrolimus. Co-administration with cyclosporine resulted in increase in apixaban maximum plasma concentration (C ) and area under the plasma concentration-time curve from time zero to the last quantifiable concentration [AUC ] with associated geometric mean ratios (GMR) and 90% confidence intervals (CI) of 143% (112, 183) and 120% (97, 148). Co-administration with tacrolimus resulted in reduction in apixaban C and AUC with associated GMRs (90% CI) of 87% (69, 112) and 78% (63, 97). The observed changes in apixaban exposure margins with cyclosporine or tacrolimus are within the range of the historical clinical development program, therefore apixaban dose adjustments are not warranted. This article is protected by copyright. All rights reserved.
PMID: 29972633 [PubMed - as supplied by publisher]