PMID: 15385835Sep 24, 2004Paper

CYP3A5 polymorphism and the ethnic differences in cyclosporine pharmacokinetics in healthy subjects

Therapeutic Drug Monitoring
David I MinHoward McLeod

Abstract

To determine the relationship between CYP3A5 polymorphism and cyclosporine pharmacokinetic parameters among healthy volunteers, an oral cyclosporine (CsA) pharmacokinetic study was performed in 16 healthy subjects. Blood CsA concentrations were measured by high-performance liquid chromatography. Concentration-versus-time data were analyzed by a noncompartmental method using WinNonLin, and the blood samples were genotyped for the CYP3A5 using the polymerase chain reaction and pyrosequencing. CsA pharmacokinetic parameters were dichotomized and compared using the 1-way ANOVA test according to the CYP3A5*3C genotype. There were 6 homozygous A/A (wild type), 6 homozygous G/G (variant), and 4 heterozygous A/G genotypes for CYP3A5*3 C in these 16 healthy volunteers. All whites were G/G group, and all African Americans except 1 were either A/A or A/G group. The mean AUC (ng x h/mL) of CsA for the 3 genotype groups were 4962 +/- 1074 (A/A), 6677 +/- 1153 (G/G), and 5416 +/- 1817 (A/G), (A/A versus G/G, P = 0.03), and the mean CL/F (mL/min/kg) were 15.6 +/- 3.1 (A/A), 12.0 +/- 2.3 (G/G), and 14.7 +/- 5.9 (A/G), (A/A versus G/G, P = 0.04). None of the other parameters were significantly different among the 3 genotypes. In conclusion, the...Continue Reading

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