title: A Randomized Controlled Trial Comparing the Efficacy of Cyp3a5 Genotype-Based With Body-Weight-Based Tacrolimus Dosing After Living Donor Kidney Transplantation.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.|Department of Hospital Pharmacy, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Shuker
authors.affiliation: Department of Hospital Pharmacy, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Bouamar
authors.affiliation: Department of Clinical Chemistry, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: R H N
authors.initials: RH
authors.lastname: van Schaik
authors.affiliation: Department of Pathology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Clahsen-van Groningen
authors.affiliation: Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Damman
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: C C
authors.initials: CC
authors.lastname: Baan
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van de Wetering
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: A T
authors.initials: AT
authors.lastname: Rowshani
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Weimar
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.|Department of Hospital Pharmacy, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: van Gelder
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: D A
authors.initials: DA
authors.lastname: Hesselink
mesh_terms: D000328:Adult; D000368:Aged; D001835:Body Weight; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications; D015995:Prevalence; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus
keywords: calcineurin inhibitor: tacrolimus; clinical research/practice; genetics; immunosuppressant; immunosuppression/immune modulation; kidney transplantation/nephrology; pharmacokinetics/pharmacodynamics