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

ABSTRACT

INTRODUCTION: Tacrolimus 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. METHODS: We 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. RESULTS: Five 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). CONCLUSION: Our 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.