人体内氟康唑的药代动力学及其生物利用度

THE PHARMACOKINETICS AND RELATIVE BIOAVAILABILITY OF FLUCONAZOLE IN HEALTHY VOLUNTEERS

以１０名健康志愿受试者对氟康唑胶囊进行了人体药代动力学及相对生物利用度试验。血浆中氟康唑的测定采用快速液－液提取（ＬＬＥ）－ＨＰＬＣ法，方法的线性范围为０．２１～５．２２ｍｇ·Ｌ－１，最低检测浓度为０．１ｍｇ·Ｌ－１，提取回收率＞７６％（ｎ＝５），方法回收率为９８．８０～１０７．５７％，日内和日间精密度分别＜８％和１３％（ｎ＝６）。结果表明：受试者交叉口服氟康唑胶囊和市售氟康唑胶囊各１５０ｍｇ后，其在人体内的药动学行为均符合零级吸收的开放一室模型，Ｔｐｅａｋ分别为１．４５±０．４４ｈ和１．４２±０．４９ｈ，Ｃｍａｘ分别为３．９６２±０．６８３ｍｇ·Ｌ－１和３．８３５±０．６０５ｍｇ·Ｌ－１，Ｔ１／２分别为３１．４９±４．５８ｈ和３０．１２±４．６３ｈ，表明氟康唑胶囊口服后具有吸收快和消除慢的特点；ＡＵＣ分别为１４０．７±１１．７ｍｇ·ｈ·Ｌ－１和１３６．７±１７．２ｍｇ·ｈ·Ｌ－１，各药物动力学参数无显著性差异（Ｐ＞０．０５）。由此算得所研制的氟康唑胶囊相对于市售氟康唑胶囊的Ｆｒｅｌ为１０２．３６±９．６１％。统计学检验结果表明，所研制的氟康唑胶囊与市售氟康唑胶囊具有生物等效性。

The pharmacokinetics and relative bioavailability of fluconazole capsules were studied in ten volunteers. Fluconazole in plasma was determined by LLE-HPLC. A linear range was from 0.21 to 5.22 mg·L-1 and the lowest limit of fluconazole in plasma was 0.1 mg·L-1. Within-day and between-day precisions were less than 8%(n=6) and 13%(n=6), respectively. The extraction recoveries were more than 76%(n=5) and the method recoveries were 98.80～107.57%. The results showed that the one-compartment open model with zero order absorption is used to describe the time course of plasma concentration of fluconazole in ten volunteers following oral administration of single dose (150 mg) of fluconazole capsule and Diflucan. The pharmacokinetics parameters were as follows: Guanghua(T): Tpeak=1.45±0.44 h, Cmax=3.962±0.68 mg·L-1, T1/2=31.49±4.58 h, AUC=140.7±11.7 mg·h·L-1; Diflucan: Tpeak=1.42±0.49 h, Cmax=3.835±0.605 mg·L-1, T1/2=30.12±4.63 h, AUC=136.7±17.2 mg·h·L-1. These pharmacokinetics parameters were no significance(P>0.05). It shows that fluconazole is well absorbed and eliminated slowly. Frel of fluconazole capsule was 102.36±9.61% and bioequivalence to Diflucan.