Pharmacokinetics of Envarsus in pediatric kidney transplant recipients – phase 1 pilot conversion study

Abstract

IntroductionTacrolimus is the standard immunosuppressant for pediatric kidney transplants and is routinely administered twice daily (BD‐tac). Envarsus (LCP‐tac), an extended‐release formulation, is approved for adults but not for pediatric patients.MethodsWe conducted a pilot open‐label phase 1 study in stable pediatric kidney transplant recipients (age < 18 at the time of study). Our primary objective was to compare the pharmacokinetics (Pk) of LCP‐tac versus BD‐tac. We conducted two 24‐h Pk studies: pre‐conversion (BD‐tac) and 4 weeks post‐conversion to LCP‐tac. Patients were followed for 6 months, with the option to continue LCP‐tac.ResultsFive patients completed the study, with no returns to BD‐tac. Median age was 15 years (range 11–17). LCP‐tac exhibited an extended‐release profile versus the bimodal profile of BD‐tac. Time to maximum concentration was delayed (5 h vs. 1 h), and maximum concentration was lower (9.9 ng/mL vs. 14.4 ng/mL). Tacrolimus area under the curve (24 h) was comparable (141 ± 46.5 ng/mL vs. 164 ± 27.8 ng/mL). No new safety concerns arose. There were no rejection and no difference in eGFR at the study's end (1.5 mL/min/1.73 m2, range − 1.7 to 2.3 mL/min/1.73 m2). Concentration/dose ratio was higher in LCP‐tac (1.8 ± 0.64 vs. 0.8 ± 0.39). The final conversion ratio was 0.6 (BD‐tac: LCP‐tac).ConclusionOur pilot study confirms the extended‐release Pk profile and improved absorption of LCP‐tac compared to BD‐tac. A larger study is needed to further evaluate the population Pk characteristics in children.