科研之友
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摘要
The aim of this study is to evaluate the association of the CYP3A4(*) 18B genotype with the cyclosporine metabolism in healthy subjects. We employed PCR RFLP assays for analysis of the CYP3A4(*)18B genotype. Each of 26 subjects, comprising 12 CYP3A4(*)1/(*)l, 12 CYP3A4(*)1/(*)18B and 2 CYP3A4(*)18B/(*)18B, was given a single oral dose of cyclosporine (4mgkg(-1)). The plasma concentrations of cyclosporine were measured for up to 24h post dose by high-performance liquid chromatography-electrospray mass spectrometry. We found that the mean C-max (95% confidence intervals) of cyclosporine were 2237 (2905, 1859) ((*)1/(*)1), 2247 (2916, 1869) ((*)1/(*)18B), and 905 (1192,506) ngml(-1) ((*)18B/(*1)8B)(p=0.037) and the mean AUCO-4were 5026 (6181, 4372) ((*)1/(*)1), 4434 (5481, 3841) ((*)1/(*)18B) and 2561 (3155, 1736) ng ml-1 h ((*)18B/(*)18B)(p=0.02l). The CL in the (*)18B/(*)18B group was significantly higher than in the (*)1/(*)1 group. However, T-maz exhibited no difference among the three genotypes. (*)18B/(*)18B group showed 50% reduction in concentration at 2h post dose compared with (*)1/(*)18B (p=0.062) or (*)1/(*)1 (p=0.047), but no statistical significance was detected between *1/(*)1 and *118B groups (p > 0.05). The data suggest that the CYP3A4(*)18B genotype affects cyclosporine pharmacokinetics probably resulting from a higher enzymatic activity of this mutation in healthy subjects.
