Increased Hospital Stay and Allograft Disfunction in Renal Transplant Recipients with Cyp2c19 AA Variant in SNP rs4244285
| Autor: | Virginia Bosó, María José Herrero, María Galiana, María Remedios Marqués, José Luis Poveda, Patricia Marrero, Julio Hernández, Salvador F. Aliño, Sergio Bea, Jaime Sánchez-Plumed |
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| Rok vydání: | 2012 |
| Předmět: |
Pharmacology
medicine.medical_specialty business.industry Pharmaceutical Science CYP2C19 medicine.disease Gastroenterology Tacrolimus Transplantation surgical procedures operative Blood drug Internal medicine medicine Adverse effect business Omeprazole Pharmacogenetics Acute tubular necrosis medicine.drug |
| Zdroj: | Drug Metabolism and Disposition. 41:480-487 |
| ISSN: | 1521-009X 0090-9556 |
| Popis: | 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 (C(min)/[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. |
| Databáze: | OpenAIRE |
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