CLINICAL IMMUNOSUPPRESSION - KIDNEY LATE

P. Burgwinkel¹, M. Wehland², S. Bauer³, S. Brakemeier⁴, P. Glander⁴, R. Kreutz³, C. Lorkowski², T. Slowinski², H.H. Neumayer⁵, K. Budde^6
1Nephrology, Charité Berlin Campus Mitte, Berlin/GERMANY, ²Nephrology, Charité Berlin, Berlin/GERMANY, ³Clinical Pharmacology, Charité Berlin, Berlin/GERMANY, ⁴Med. Klinik Mit Sp Nephrologie, Charite - Campus Mitte, Berlin/GERMANY, ⁵, Charité, Humboldt University, Berlin/GERMANY, ⁶Medizinische Klinik, Universitätsklinik Charité, Berlin/GERMANY

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We investigated pharmacokinetic and pharmacogenetic implications of conversion from a twice-daily tacrolimus (Tac) formulation (P-Tac) to the once-daily Tac formulation (A-Tac) in a cohort of 41renal transplant patients with stable graft function. After conversion from P-Tac to A-Tac patients had on average significantly lower Tac trough and dose-normalized trough levels (14%, P=0.0004 and23%, P=0.001, respectively) despite similar Tac doses. Because of large interindividual differences we investigated the influence of the CYP3A5*1/*3 polymorphism on Tac pharmacokinetics. Homozygous*3/*3 patients (n=27) required significantly lower Tac doses with both formulations to reach Tac target levels (P-Tac 39%, P=0.011; A-Tac 36%, P=0.003) compared to heterozygous *1/*3 patients (n=13).Interestingly, mean Tac trough levels and dose-normalized Tac trough levels remained almost constant in carriers of CYP3A5*1 after conversion from P-Tac to A-Tac, however decreased significantly innon-carriers of CYP3A5*1 after conversion (16%, P=0.001 and 25%, P=0.006). This study provides further evidence that the CYP3A5*1/*3 polymorphism has a significant impact on Tac pharmacokinetics.Moreover, we show for the first time a pharmacogenetic effect on two different Tac formulations, as non-carriers of CYP3A5*1 had a significant decline of Tac trough levels after conversion to A-Tacwhen the dose remained unchanged

Disclosure: All authors have declared no conflicts of interest.