Author(s): Terrault NA, Tran TT, Schiff E, McGuire BM, Brown RS Jr,
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Abstract 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.
This article was published in Liver Int
and referenced in Journal of Antivirals & Antiretrovirals