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

Autor: Rachida Bouamar, Dennis A. Hesselink, Nauras Shuker, Ajda T. Rowshani, Willem Weimar, J. van de Wetering, Carla C. Baan, T. van Gelder, R.H.N. van Schaik, M. C. Clahsen-van Groningen, Jeffrey Damman
Přispěvatelé: Internal Medicine, Pharmacy, Clinical Chemistry, Pathology, Other departments
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Graft Rejection
Male
030230 surgery
Pharmacology
Kidney Function Tests
030226 pharmacology & pharmacy
Gastroenterology
law.invention
0302 clinical medicine
Postoperative Complications
Randomized controlled trial
law
Risk Factors
Living Donors
Prevalence
Immunology and Allergy
Cytochrome P-450 CYP3A
Pharmacology (medical)
Prospective Studies
Kidney transplantation
Netherlands
education.field_of_study
Incidence (epidemiology)
Graft Survival
Middle Aged
Prognosis
surgical procedures
operative
Female
Immunosuppressive Agents
Glomerular Filtration Rate
Adult
medicine.medical_specialty
Genotype
Population
chemical and pharmacologic phenomena
Polymorphism
Single Nucleotide
Tacrolimus
03 medical and health sciences
Young Adult
Internal medicine
medicine
Humans
Dosing
education
Aged
Transplantation
Dose-Response Relationship
Drug
business.industry
Body Weight
medicine.disease
Kidney Transplantation
Kidney Failure
Chronic
business
Pharmacogenetics
Follow-Up Studies
Zdroj: American Journal of Transplantation, 16(7), 2085-2096. Wiley-Blackwell Publishing Ltd
American journal of transplantation, 16(7), 2085-2096. Wiley-Blackwell
ISSN: 1600-6135
DOI: 10.1111/ajt.13691
Popis: 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 thetarget tacrolimus predose concentration range (10-15ng/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. 15ng/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 dosedoes 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. This randomized trial shows that in living donor kidney transplant recipients, a tacrolimus starting dose based on the CYP3A5 genotype does not increase the proportion of patients reaching the tacrolimus target concentration range at day 3 posttransplant.
Databáze: OpenAIRE
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