Pharmacokinetics of tacrolimus co-administered with adefovir dipivoxil to liver transplant recipients

Academic Article

Abstract

  • Background: Adefovir dipivoxil has activity against wild-type and lamivudineresistant hepatitis B virus (HBV) and is frequently used to manage HBV infection in transplant recipients. Calcineurin inhibitors are a central component of immunosuppressive therapy. Aims: Study GS-02-531 was an openlabel, multicentre drug interaction trial to examine potential drug interactions between adefovir and tacrolimus in stable post-transplant recipients. Materials and Methods: Sixteen non-HBV-infected post-transplant recipients with median age 45.5 years (69% male, 44% Caucasian, 50% Hispanic and 6% Black) and stable hepatic and renal function on a stable daily dose of tacrolimus (2-10 mg total daily dose) were studied before (tacrolimus alone) and after co-administration of adefovir 10 mg daily for 14 days (Days 1-14). Pharmacokinetic (PK) analyses utilized non-compartmental methods. Results: The median elimination half-life of tacrolimus was 14.47 and 12.59 h for Day 0 and Day 14 respectively. The geometric mean ratios for tacrolimus on Day 14 vs Day 0 were 105.2% [90% confidence interval (90% CI): 89.8-123%] for Cmax and 106.4% (90% CI: 92.9-122%) for AUCtau. Both 90% CIs for the ratios were contained within the predefined lack of interaction bounds of 80 and 125% (i.e. within the bounds for the equivalence assessment), indicating that these PK parameters of tacrolimus are not significantly altered by co-administration of adefovir. Similarly, the observed adefovir PK parameters after 14 days of co-administration with tacrolimus were comparable to historical data in non-transplant patients receiving adefovir alone. Serum creatinine values were stable during the study period. Conclusion: There is no significant PK interaction between tacrolimus and adefovir co-administered to liver transplant recipients for 14 days. © 2009 John Wiley & Sons A/S.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Terrault NA; Tran TT; Schiff E; McGuire BM; Brown RS; Tupper R; Ramanathan S; Enejosa J; Zhong L; Zong J
  • Start Page

  • 1178
  • End Page

  • 1183
  • Volume

  • 29
  • Issue

  • 8