Patients expressing the cytochrome P450 (CYP) 3A5 gene require a higher tacrolimus dose to achieve therapeutic exposure compared with non-expressers. This randomized-controlled study investigated if adaptation of the tacrolimus starting dose according to CYP3A5 genotype increases the proportion of kidney transplant recipients being within the target tacrolimus predose concentration range (10-15 ng/mL) at first steady-state. Two hundred forty living-donor, renal transplant recipients were assigned to either receive a standard, bodyweight-based or a CYP3A5 genotype-based tacrolimus starting dose. At day 3, no difference in the proportion of patients having a tacrolimus exposure within the target range was observed between the standard-dose and genotype-based groups: 37.4% vs. 35.6%, respectively; p = 0.79. The proportion of patients with a sub-therapeutic (i.e. <10 ng/mL) or a supra-therapeutic (i.e. >15 ng/mL) Tac C₀ in the two groups was also not significantly different. The incidence of acute rejection was comparable between both groups: 10.1% and 11.0% for the standard bodyweight-based and genotype-based groups, respectively; p = 0.82. Pharmacogenetic adaptation of the tacrolimus starting dose does not increase the number of patients having therapeutic tacrolimus exposure early after transplantation and does not lead to improved clinical outcome in a low immunological risk population.

CITATION INFORMATION: Shuker N, Bouamar R, van Schaik R, Clahsen -van Groningen M, Damman J, Baan C, van de Wetering J, Rowshani A, Weimar W, van Gelder T, Hesselink D. A Randomized-Controlled Trial Comparing the Efficacy of CYP3A5 Genotype-Based with Bodyweight-Based Tacrolimus Dosing After Living Donor Kidney Transplantation. Am J Transplant. 2016;16 (suppl 3).

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