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

Background: Adefovir dipivoxil has activity against wild‐type and lamivudine‐resistant 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 open‐label, 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 C max and 106.4% (90% CI: 92.9–122%) for AUC tau . 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.