A Randomized Controlled Trial Comparing the Efficacy of Cyp3a5 Genotype-Based With Body-Weight-Based Tacrolimus Dosing After Living Donor Kidney Transplantation.

Autor: Shuker N; Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.; Department of Hospital Pharmacy, Erasmus Medical Centre, Rotterdam, The Netherlands., Bouamar R; Department of Hospital Pharmacy, Erasmus Medical Centre, Rotterdam, The Netherlands., van Schaik RH; Department of Clinical Chemistry, Erasmus Medical Centre, Rotterdam, The Netherlands., Clahsen-van Groningen MC; Department of Pathology, Erasmus Medical Centre, Rotterdam, The Netherlands., Damman J; Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands., Baan CC; Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands., van de Wetering J; Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands., Rowshani AT; Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands., Weimar W; Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands., van Gelder T; Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.; Department of Hospital Pharmacy, Erasmus Medical Centre, Rotterdam, The Netherlands., Hesselink DA; Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
Jazyk: angličtina
Zdroj: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2016 Jul; Vol. 16 (7), pp. 2085-96. Date of Electronic Publication: 2016 Feb 26.
DOI: 10.1111/ajt.13691
Abstrakt: Patients expressing the cytochrome P450 (CYP) 3A5 gene require a higher tacrolimus dose to achieve therapeutic exposure compared with nonexpressers. This randomized-controlled study investigated whether 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, body-weight-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% versus 35.6%, respectively; p = 0.79. The proportion of patients with a subtherapeutic (i.e. <10 ng/mL) or a supratherapeutic (i.e. >15 ng/mL) Tac predose concentration in the two groups was also not significantly different. The incidence of acute rejection was comparable between both groups (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.
(© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)
Databáze: MEDLINE
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