Kidney Transplant Recipients Carrying the CYP3A4*22 Allelic Variant Have Reduced Tacrolimus Clearance and Often Reach Supratherapeutic Tacrolimus Concentrations. Issue 3 (14th January 2015)

• Record Type: Journal Article
• Authors: Pallet, N.; Jannot, A.‐S.; El Bahri, M.; Etienne, I.; Buchler, M.; de Ligny, B. H.; Choukroun, G.; Colosio, C.; Thierry, A.; Vigneau, C.; Moulin, B.; Le Meur, Y.; Heng, A.‐E.; Subra, J.‐F.; Legendre, C.; Beaune, P.; Alberti, C.; Loriot, M. A.; Thervet, E.
• Is Part Of: American journal of transplantation. Volume 15:Issue 3(2015:Mar.)
• Page Start: 800
• Page End: 805
• Publication Date: 2015-01-14
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.13059
• Languages: English
• ISSNs: 1600-6135

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajt13059-sec-0001" sec-type="section"> <p> <italic>CYP3A4*22</italic> is an allelic variant of the cytochrome P450 3A4 associated with a decreased activity. Carriers of this polymorphism may require reduced tacrolimus (Tac) doses to reach the target residual concentrations (Co). We tested this hypothesis in a population of kidney transplant recipients extracted from a multicenter, prospective and randomized study. Among the 186 kidney transplant recipients included, 9.3% (18 patients) were heterozygous for the <italic>CYP3A4*22</italic> genotype and none were homozygous (allele frequency of 4.8%). Ten days after transplantation (3 days after starting treatment with Tac), 11% of the <italic>CYP3A4*22</italic> carriers were within the target range of Tac Co (10–15 ng/mL), whereas among the <italic>CYP3A4*1/*1</italic> carriers, 40% were within the target range (p = 0.02, OR = 0.19 [0.03; 0.69]). The mean Tac Co at day 10 in the <italic>CYP3A4*1/*22</italic> group was 23.5 ng/mL (16.6–30.9) compared with 15.1 ng/mL (14–16.3) in the <italic>CYP3A4*1/*1</italic> group, p < 0.001. The Tac Co/dose significantly depended on the <italic>CYP3A4</italic> genotype during the follow‐up (random effects model, p < 0.001) with the corresponding equivalent dose for patients heterozygous for <italic>CYP3A4*22</italic> being 0.67 [0.54; 0.84] times the dose for <italic>CYP3A4*1/*1</italic> carriers. In conclusion, the <italic>CYP3A4*22</italic> allelic variant is associated with a significantly altered Tac metabolism and carriers of this polymorphism often reach supratherapeutic concentrations.</p> </sec> </abstract>