盐酸黄连素对肾移植受者环孢素A增效作用的临床药代动力学研究

The Pharmacokinetics of Enhancement of Cyclosporin A by Berberine Chloride Coadministrated in Renal Transplanted Recipients

目的：研究盐酸黄连素对肾移植受者使用环孢素Ａ增效作用的体内动力学过程。方法：选择肾移植术后１个月以内、连续服用环孢素Ａ２周、肝肾功能稳定的患者６名，环孢素Ａ剂量６ｍｇ．ｋｇ－４．ｄ－１，用ＦＰＩＡ方法（单抗）检测合用黄连素前后各时间点环孢素Ａ全血浓度。结果：单服环孢素Ａ的主要药代动力学参数分别为ｔｍａｘ（ｈ）：１．３３±０．５２，Ｃｍａｘ（μｇ·Ｌ－１）：１２２４．７５±２９６．２０，Ｃｍｉｎ（μｇ·Ｌ－１）：１７３．９５±７８．７１，ｔ１／２（ｈ）：２．６２±１．００，ＡＵＣμｇ·ｈ·Ｌ－１４６８１．３４±１３００．４５，ＣＬ／Ｆ（Ｌ·ｈ－１）：３５±１５；与黄连素合用的主要药代动力学参数为ｔｍａｘ（ｈ）：３．００±１．２６Ｃｍａｘ（μｇ·Ｌ－１）：１０５０．１０±２９０．８６，Ｃｍｉｎ（μｇ·Ｌ－１）：３２１．３１±１６１．２９，ｔ１／２（ｈ）：５．３３±２．６０，ＡＵＣμｇ·ｈ·Ｌ－１６２６５．７１±１８７１．３３，ＣＬ／Ｆ（Ｌ·ｈ－１）：２２±１３。结论：盐酸黄连素与环孢素Ａ合用可使后者ｔｍａｘ滞后，ｔ１／２延长，清除率减少，ＡＵＣ增大，生物利用度增加；对肝肾功能没有影响。

OBJECTIVE: To study the pharmacokinetics of cyclosporin A (CsA) with or without combination of berberine chloride(Ber)in renal transplanted recipients. METHODS:This study included 6 patients treated with cyclosporin A at 6 mg.g-1d-1 for two weeks within one month of renal transplantation. Each patient was involved in pharmacokinetics of cyclosporin A before and after coadministration of berberine hydrochride by fluorescence polarization immunoassay. RESULTS: The pharmacokinetic parameters of cyclosporin A before coadministration of berberine were:t(1/2):2.62±1.OOh,tmax:1.33±0.52h,Cmax:1224.75±296.20μg.L-1, Cmin:173.95 ±78.71μg.L-1,AUC: 4681.34±1300.45μg.h.L-1,CL/F: 35±15L.h-1.The pharmacokinetic parameters of cyclosporin A after coadministration of berberine hydro chloride were: t(1/2): 5.33±2.6,AUC:6265.71±1871.33μg.h.L-1,CL/F:22± 13L.h-1. CONCLUSION: berberine hydro chloride could markedly elevate the blood concentration of cyclosporin A in renal transplanted recipients. After coadministration of berberine hydro chloride, tmax of cyclosporin A was delayed and CL was decreased while t1/2, and A UC were increased. Two drug coadministration had no effects on liver and renal function.