PT  - JOURNAL ARTICLE
AU  - Virginia Bosó
AU  - María José Herrero
AU  - Sergio Bea
AU  - María Galiana
AU  - Patricia Marrero
AU  - María Remedios Marqués
AU  - Julio Hernández
AU  - Jaime Sánchez-Plumed
AU  - José Luis Poveda
AU  - Salvador F. Aliño
TI  - Increased Hospital Stay and Allograft Disfunction in Renal Transplant Recipients with Cyp2c19 AA Variant in SNP rs4244285
AID  - 10.1124/dmd.112.047977
DP  - 2013 Feb 01
TA  - Drug Metabolism and Disposition
PG  - 480--487
VI  - 41
IP  - 2
4099  - http://dmd.aspetjournals.org/content/41/2/480.short
4100  - http://dmd.aspetjournals.org/content/41/2/480.full
SO  - Drug Metab Dispos2013 Feb 01; 41
AB  - Pharmacogenetics correlates certain genetic variants, such as single nucleotide polymorphisms (SNPs), with blood drug levels, efficacy, and adverse effects of the treatment. Tacrolimus is mainly metabolized via CYP3A4/5, whereas CYP2C19 and CYP3A4/5 are responsible for omeprazole metabolism. Omeprazole inhibits tacrolimus metabolism via CYP3A5 in patients carrying variant alleles of CYP2C19, increasing tacrolimus blood concentrations. Seventy-five renal transplant recipients treated with tacrolimus and concomitant omeprazole were genotyped in a panel of 37 SNPs with use of Sequenom MassArray. The patients with CYP2C19*2/*2 genotype (n = 4) showed a median posttransplantation hospital stay of 27.5 days (95% confidence interval [CI], 23–39 days), compared with 12 days (95% CI, 10–15 days) in patients with CYP2C19*1/*1 or CYP2C19*1/*2 (n = 71; P = 0.016, Kruskal-Wallis test).The difference in hospital stay was directly correlated with an increase in tacrolimus levels (Cmin/[dose/weight]) during the first week after trasplantation (in 59 patients with data on levels; P = 0.021, Kruskal-Wallis), excluding the patients with atypical metabolisms due to CYP3A5*1/*3 or CYP3A5*1/*1 genotype. Recipients with CYP2C19*2/*2 genotype also showed allograft delayed function (acute tubular necrosis in 3 patients). Genotyping of CYP3A5 and CYP2C19 in renal transplantation should be considered to be of interest when treating with tacrolimus and omeprazole, because CYP2C19*2/*2 variant indirectly elicits an increase of tacrolimus blood levels and, in our study population, the adverse effects described.