Influence of the MDR1 haplotype and CYP3A5 genotypes on cyclosporine blood level in Chinese renal transplant recipients.
The purpose of the study was to elucidate the influence of multidrug resistance gene (MDR1) haplotype and CYP3A5 genotype on cyclosporine (CsA) blood level in Chinese renal transplant recipients. CsA trough level (C(0)) and peak level (C(2)) of 115 patients 1 week and 1 month after renal transplantation were determined. MDR1 C1236T, G2677T/A, C3435T and CYP3A5*3 genotypes were determined by polymerase chain reaction (PCR) assays based on amplification refractory mutation. Dose-adjusted C(0) (C(0)/D), C(2) (C(2)/D) were 50.5 +/- 22.5, 267.8 +/- 110.1 ng.kg.(ml.mg)(-1) after 1 week of therapy, and 79.3 +/- 29.4, 406.0 +/- 135.3 ng.kg.(ml.mg)(-1) after 1 month of therapy. Frequencies of MDR1 haplotype TTT, CGC, and TGC were 27.0%, 25.2% and 20.0%, respectively. After 1 month of therapy, C(2)/D of TTT/TTT patients were 30% (p = 0.057) and 53% (p = 0.003) higher than CGC/TTT and CGC/CGC patients. C(0)/D of CYP3A5 *1/*1, *1/*3 and *3/*3 patients after 1 month of therapy were 51.8 +/- 25.0, 71.5 +/- 27.6, and 86.7 +/- 28.6 ng.kg.(ml.mg)(-1) (p < 0.05). MDR1 haplotypes and CYP3A5*3 genotypes can be related to C(2) and C(0) of CsA, respectively.
Chen
B
B
Department of Clinical Pharmacology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Zhang
W
W
Fang
J
J
Jin
Z
Z
Li
J
J
Yu
Z
Z
Cai
W
W
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D019540:Area Under Curve; D044466:Asian People / Q000235:genetics*; D016572:Cyclosporine / Q000097:blood*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D003710:Demography; D004305:Dose-Response Relationship, Drug; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D055815:Young Adult
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016572:Cyclosporine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A