Impact of donor and recipient CYP3A5 and ABCB1 genetic polymorphisms on tacrolimus dosage requirements and rejection in Caucasian Spanish liver transplant patients. (11th September 2013)

• Record Type: Journal Article
• Authors: Gómez‐Bravo, Miguel Angel; Salcedo, Magdalena; Fondevila, Constantino; Suarez, Francisco; Castellote, José; Rufian, Sebastián; Pons, José Antonio; Alamo, José María; Millán, Olga; Brunet, Mercè
• Is Part Of: Journal of clinical pharmacology. Volume 53:Number 11(2013:Nov.)
• Page Start: 1146
• Page End: 1154
• Publication Date: 2013-09-11
• Subjects: Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1002/jcph.154
• Languages: English
• ISSNs: 0091-2700

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="jcph154-sec-0001" sec-type="section"> <p>Studies of liver transplant (LT) patients, mainly in Asians, have evaluated the influence of the <italic>CYP3A5*1</italic> allele and P‐glycoprotein gene <italic>ABCB1</italic> on tacrolimus pharmacokinetics or biopsy‐proven acute rejection (BPAR) incidence, with no conclusive results. To investigate these issues, 98 Caucasian Spanish LT patients with tacrolimus, mycophenolate mofetil and steroids and 88 cadaveric donors were genotyped for the SNPs <italic>CYP3A5</italic> 6986G>A, <italic>ABCB1</italic> 1236C>T, <italic>ABCB1</italic> 2677G>A/T and <italic>ABCB1</italic> 3435C>T;. On day 7 post‐LT, patients with a native <italic>CYP3A5*1</italic> allele had significantly lower tacrolimus trough concentrations C<sub>0</sub> (<italic>P</italic> = .03) and dose‐adjusted concentrations C<sub>0</sub>/D (<italic>P</italic> = .02) than <italic>CYP3A5 *3/*3</italic> homozygotes. Three months post‐LT, patients carrying a liver with <italic>CYP3A5*1</italic> had significantly lower C<sub>0</sub>/D (<italic>P</italic> = .03) and took significantly higher tacrolimus doses (<italic>P</italic> = .03) than the corresponding <italic>*3/*3</italic> homozygotes. <italic>ABCB1</italic> SNPs showed no significant association with tacrolimus variables. The 3‐month incidence of BPAR was 10.2%, with no statistically significant differences related to <italic>CYP3A5</italic> (14.3% in expresser vs. 9.5% in non‐expresser) or <italic>ABCB1</italic> genotype of either patient or donor. We conclude that in Caucasian Spanish LT patients, a native or graft‐borne <italic>CYP3A5*1</italic> allele tends to lower tacrolimus concentrations and increase dosage needs, but has no significant impact on the incidence of BPAR.</p> </sec> </abstract>