کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5809855 | 1556174 | 2015 | 7 صفحه PDF | دانلود رایگان |
AimCyclosporine is an immunosuppressant drug used to prevent allograft rejection. It is metabolized by CYP3A4 and CYP3A5, has a narrow therapeutic index, and variable pharmacokinetics. Here, we investigated whether CYP3A5â3 and CYP3A4â18B polymorphisms contribute to inter-individual pharmacokinetic variability in healthy subjects.Patients and methodsFifty-six healthy Chinese subjects were enrolled in the study after signing a written consent. The subjects received 5 mg kgâ1 of cyclosporine orally and were genotyped for CYP3A5â3 and CYP3A4â18B using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Blood concentrations of cyclosporine were measured by high-performance liquid chromatography for up to 30 h post-dose.ResultsThe mean cyclosporine AUC0â30 and AUC0ââ in the male group was significantly higher than that in the female group (P = 0.037 and 0.035); the CL/F in the male group was significantly lower than that in the female group (P = 0.033). The Cmax of cyclosporine in CYP3A4â1/â1 was significantly greater than that in CYP3A4â1/â18B in the male group (P = 0.023), but not the female group. In addition, the Cmax in CYP3A5â1/â3 was significantly lower than that in CYP3A5â3/â3 in the male group (P = 0.01).ConclusionsThe results indicate that gender and polymorphism in CYP3A4â18B and CYP3A5â3 significantly affect cyclosporine pharmacokinetics in healthy subjects.
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Journal: European Journal of Pharmaceutical Sciences - Volume 76, 30 August 2015, Pages 238-244