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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lee, Jun Huang, Hongfeng Chen, Ying Lu, Xiaoyang |
| Description | Country affiliation: China Author Affiliation: Lee J ( Department of Clinical Pharmacology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.) |
| Abstract | Sirolimus, an immunosuppressive drug used to prevent organ rejection after renal transplantation, has a narrow therapeutic index and a large inter-individual variability of pharmacokinetics. The aim of this study was to analyse the dose-normalized trough blood concentrations (C0 /D ratio) of sirolimus in patients with different genotypes and attempt to investigate the possible associations between ABCB1/CYP3A5 genotypes and sirolimus dose requirements in Chinese renal transplant recipients. Blood samples were collected from 85 Chinese renal transplant recipients who were treated with sirolimus for at least 3 months and polymorphisms of the ABCB1 and CYP3A5 were determined by the SNaPShot multiplex assay. The blood concentrations of sirolimus were determined with HPLC. A significant allele-dependent effect was observed between the CYP3A5*3 polymorphism and the C0 /D ratio of sirolimus. The patients bearing at least one CYP3A5*1 allele had a lower sirolimus C0/D ratio compared with those with a homozygous CYP3A5*3 genotype (p < 0.05). No significant differences of sirolimus C0/D ratios were observed among various ABCB1 1236C>T, 2677G>T/A and 3435C>T genotype groups. However, haplotype analysis including ABCB1 1236C>T, 2677G>T/A and 3435C>T SNPs showed that the mean sirolimus C0/D of subjects carrying the CGC/CGC diplotype was about 30% lower compared with those carrying the CGC/TTT or TTT/TTT diplotype, whether or not they expressed the CYP3A5 (p < 0.05). These results demonstrated that the haplotype of ABCB1 might be a better index for the prediction of sirolimus blood concentration than single SNPs. Genotyping of ABCB1 and CYP3A5 might help to optimize individualized sirolimus treatments for Chinese renal transplant recipients. |
| File Format | HTM / HTML |
| ISSN | 01422782 |
| Issue Number | 3 |
| Volume Number | 35 |
| e-ISSN | 1099081X |
| Journal | Biopharmaceutics & Drug Disposition |
| Language | English |
| Publisher | Wiley |
| Publisher Date | 2014-04-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Pharmacology Immunosuppressive Agents Administration & Dosage Kidney Transplantation Methods Sirolimus Adult Asian Continental Ancestry Group Chromatography, High Pressure Liquid Cytochrome P-450 Cyp3a Genetics Dose-response Relationship, Drug Female Genotype Haplotypes Humans Pharmacokinetics Male Middle Aged P-glycoproteins Polymorphism, Single Nucleotide Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Pharmacology (medical) Pharmaceutical Science |
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