国产多奈哌齐胶囊人体药代动力学和相对生物利用度研究

Study of the Pharmacokinetics and Bioequivalance of Domestic Donepezil in Healthy Chinese Volunteers

目 的：建立测定多奈哌齐血浆药物浓度的ＨＰＬＣ－ＵＶ检测法，研究国产多奈派齐胶囊在人体的药代动力学和相对生物利用度。方法：２４名健康男性志愿受试者单剂量随机交叉口服５ｍｇ国产多奈派齐胶囊和进口多奈哌齐片，采用ＨＰＬＣ法测定给药后不同时间点血浆中多奈派齐浓度，运用３Ｐ９７程序拟合房室模型，技统计矩进行药代动力学参数计算，并作方差分析和双维侧ｔ检验。结果：国产和进口多奈派齐的血药浓度－时间曲线符合二室开放模型，其主要药代动力学参数：Ｃｍаｘ分别为 １１．８５± ２．４７与１１．４８±２．８５μｇ·Ｌ－１（Ｐ＞０．０５），ｔｍаｘ分别为２．４３±０．５８与２．４６±０．５７ ｈ（Ｐ＞０．０５），ｔ１／２β分别为 ５１．５２± １４．１９与５４．５５±１４．２９ｈ（Ｐ＞０．０５）；ＡＵＣ０－１分别为４１７．９７±９０．７１和３９４．０６±９１．４０μｇ·Ｌ－１（Ｐ＞０．０５）。国产胶囊对进口片剂的相对生物利用度（Ｆ）为１０８．７４％±２１．８７％，国产多奈哌齐胶囊和进口片剂主要药代动力学参数均无显著性差异（Ｐ＞０．０５）。结论：双单侧ｔ检验结果显示国产多奈哌齐胶囊和进口多奈哌齐片生物等效。

OBJECTIVE: A HPLC-UV method was developed and validated to determine donepezil in human plasma and study the pharmacokinetics profiles and bioequivalence of domestic and imported donepezil capsules in 24 healthy volunteers. METHODS: Single oral dose (5mg) of domestic and imported donepezil were given to 24 healty male volunteers in an open randomized cross-over study. Donepezil concentrations in plasma were determined by HPLC method. The pharmacokinetic parameters as well as relative bioavailability were measured. RESULTS: The concentration-time curves of donepezil were conformed to an two-compartment open model.The main pharmacokinetic parameters of domestic and imported preparations were as follows: Cmax were 11.85± 2.47 and 11.48±2.85μg·L-1(P>0.05), tmax were 2.43±0.58 and 2.46±0.57 h (P>0.05,t1/2β were 51.52 ±14. 19 and 54.55±14.29h (P>0.05); AUC0-1 were 417.97±90.71 and 394.06 ±91.40μg·h·L-1 (P>0.05), respectively. There were no significant difference between the two formulations. The relative bioavailability of domestic donepezil capsule was 108.74%±21.87%. CONCLUSION: The result of the statistical analysis showed that the two formulations were bioequivalent.