Details

Autor(en) / Beteiligte

• Qiu, Xiao-yan
• Jiao, Zheng
• Zhang, Ming
• Zhong, Long-jin
• Liang, Hui-qi
• Ma, Chun-lai
• Zhang, Liang
• Zhong, Ming-kang

Titel

Association of MDR1, CYP3A418B, and CYP3A53 polymorphisms with cyclosporine pharmacokinetics in Chinese renal transplant recipients

Ist Teil von

• European journal of clinical pharmacology, 2008-11, Vol.64 (11), p.1069-1084

Ort / Verlag

Berlin/Heidelberg: Springer-Verlag

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• Objective The objective of this study was to retrospectively evaluate the effects of MDR1, CYP3A4*18B, and CYP3A5*3 genetic polymorphisms on cyclosporine A (CsA) pharmacokinetics in Chinese renal transplant patients during the first month after transplantation. Methods A total of 103 renal transplant recipients receiving CsA were genotyped for MDR1 (C1236T, G2677T/A, and C3435T), CYP3A4*18B, and CYP3A5*3. The predose and 2-h postdose concentrations of CsA (C 0 and C 2 , respectively) were determined by fluorescence polarization immunoassay, and their relationships with corresponding genotypes and haplotypes were investigated. Results Patients with a CYP3A4*1/*1 genotype were found to have a higher dose-adjusted concentration compared with those with CYP3A4*18B/*18B, as follows: for C 2 , 19.3% ( P  = 0.008) during days 8-15, 35.2% ( P  = 0.008) during days 16–30, and for C 0 , 39.7% ( P  = 0.012) during days 16–30. The dose-adjusted C 0 was higher in patients with MDR1 1236CC compared with those with 1236TT in the first month postoperation. The dose-adjusted C 0 in patients with the CYP3A5*3/*3 genotype was 25.5% and 30.7% higher than those with the wild-type genotype during days 8–15 ( P  = 0.011) and days 16–30 ( P  = 0.015), respectively. Haplotype analysis revealed that the dose-adjusted C 0 was higher in the first month following surgery in carriers of haplotype MDR1 CAC than in noncarriers. Polymorphisms of MDR1 and CYP3A5*3 did not affect dose-adjusted C 2. Conclusion The data suggests that the CYP3A4*18B genotype affects CsA pharmacokinetics during the first month following surgery in Chinese renal transplant recipients. Patients with CYP3A4*18B alleles may require higher doses of CsA to reach the target levels. Large prospective studies may be needed to further explore the impact of MDR1 and CYP3A5*3 polymorphisms on CsA pharmacokinetics in renal transplant recipients.