期刊
THERAPEUTIC DRUG MONITORING
卷 24, 期 3, 页码 400-404出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00007691-200206000-00012
关键词
MDR1 gene mutation; P-glycoprotein; cyclosporine; pharmacokinetics
资金
- NCRR NIH HHS [RR 00059] Funding Source: Medline
To determine the relationship between C3435T mutation in exon 26 of the human multidrug resistant 1 (MDR1) gene and cyclosporine pharmacokinetic parameters among healthy volunteers, the oral cyclosporine pharmacokinetic study was performed for 14 healthy subjects, Blood cyclosporine concentrations were measured by HPLC. Concentration-time data were analyzed by a noncompartmental method using WinNonLin, and the blood samples were genotyped for the C3435T polymorphism of MDR1 gene using the PCR and a restriction digest. Each cyclosporine pharmacokinetic parameter was compared using the Mann-Whitney U test according to his or her P-gp genotype. There were seven (7) homozygous Cl, six (6) C/T, and one (1) homozygous T/T genotypes in these 14 healthy volunteers. According to their genotypes, mean t(max) 1.6+/-0.3 hours, mean C-max 1337+/-329 ng/mL, mean Cl/F 66.5+/-18.3 L/h, and mean AUC 5642+/-1577 ng.h/mL in C1/F group and mean t(max) 2.0+/-0.6 hours, mean C-max 1540+/-721 ng/mL, mean Cl/F 55.2+/-18.9 L/h, and mean AUC 6902+/-1405 ng.h/mL in C/T+T/T group. Although C-max and AUC in C/T and T/T group were 15% and 227c larger than those in C/C group, none of these parameter comparisons was statistically significant. There were no statistical differences in cyclosporine pharmacokinetics among different MDR1 genotypes in these 14 healthy subjects.
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