Factors affecting the long-term response to tacrolimus in renal transplant patients: Pharmacokinetic and pharmacogenetic approach Journal Article
| Authors: | Katsakiori, P. F.; Papapetrou, E. P.; Sakellaropoulos, G. C.; Goumenos, D. S.; Nikiforidis, G. C.; Flordellis, C. S. |
| Article Title: | Factors affecting the long-term response to tacrolimus in renal transplant patients: Pharmacokinetic and pharmacogenetic approach |
| Abstract: | Background: The aim of our study was to determine the impact of CYP3A5*1 and CYP3A5*3 on the kinetics of tacrolimus in renal transplant recipients. Material and methods: Forty kidney recipients were selected to participate. Maintenance scheme consisted of tacrolimus, a purine inhibitor and a steroid. CYP3A5 genotyping was performed with PCR and RFLP. Pharmacokinetic model was developed with Linear Regression and General Linear Model repeated measures approach. The impact of sex, CYP3A5*1 allele, age at transplantation, hepatic and renal function on tacrolimus kinetics was examined. Results: The frequency of CYP3A5*3/*3 and CYP3A5*1/*3 genotype was 35/40 and 5/40, respectively. No CYP3A5*1/*1 was detected. CYP3A5*1 variant was associated with significant lower TAC dose adjusted concentration at 3, 6, 12 and 36 months after transplantation. Hepatic and renal function showed a significant effect on tacrolimus dose adjusted concentration 3 months after transplantation (p=0.000 and 0.028, respectively). Sex did not show a significant impact on tacrolimus kinetics. Carriers of CYP3A5*1 allele had lower predicted measures for tacrolimus dose adjusted concentration and higher predicted measures for volume of distribution. Conclusion: We proved that CYP3A5*1 carriers need higher tacrolimus dose than CYP3A5*3 homozygotes to achieve the target blood concentration. © Ivyspring International Publisher. |
| Keywords: | adolescent; adult; clinical article; aged; middle aged; dose response; liver function; polymerase chain reaction; allele; genotype; alleles; gene frequency; steroid; drug effect; prednisolone; blood; kidney; drug distribution; kidney function; drug response; homozygote; azathioprine; pharmacogenetics; drug blood level; kidney function test; tacrolimus; mycophenolic acid 2 morpholinoethyl ester; graft recipient; kidney graft rejection; kidney transplantation; linear regression; kidney function tests; steroids; cyp3a5; general linear models; renal transplantation; cytochrome p450 3a5; cyp3a5 protein, human; cytochrome p450 3a; kidney graft; restriction fragment length polymorphism; cytochrome p-450 cyp3a; polymorphism, restriction fragment length |
| Journal Title: | International Journal of Medical Sciences |
| Volume: | 7 |
| Issue: | 2 |
| ISSN: | 1449-1907 |
| Publisher: | Ivyspring International Publisher |
| Date Published: | 2010-05-11 |
| Start Page: | 94 |
| End Page: | 100 |
| Language: | English |
| PUBMED: | 20479955 |
| PROVIDER: | scopus |
| PMCID: | PMC2869454 |
| DOI: | 10.7150/ijms.7.94 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "Source: Scopus" |
