空腹或餐后服用国产伊曲康唑胶囊的人体生物等效性研究

Study on bioequivalence of domestic Itraconazole capsules before or after diet

目的:评价健康男性志愿者空腹或餐后单次口服国产伊曲康唑胶囊与进口伊曲康唑胶囊(商品名为斯皮仁诺胶囊)的生物等效性。方法:本研究包括两个随机、开放、双周期、单次口服给药试验,各入组24名健康中国男性受试者,分别在空腹和餐后服用200mg试验制剂和200mg参比制剂后,采用HPLC-MS/MS方法测定给药后伊曲康唑的血药浓度。计算主要药动学参数,分别对两种制剂的空腹或餐后给药进行生物等效性评价。结果:空腹给药试验制剂与参比制剂的主要药动学参数为:Cmax为(124±79)和(124±86)μg/L;tmax为(2.9±0.8)和(2.5±0.9)h;AUC0-t为(1320±826)和(1348±1095)μg.h.L-1;AUC0-∞为(1420±902)和(1444±1148)μg.h.L-1;AUC0-t/AUC0-∞为(93.0±4.9)和(92.3±5.1)%;t1/2为(17.7±4.7)和(18.1±2.8)h。空腹给药试验制剂的相对生物利用度F为(106.5±35.4)%。餐后给药试验制剂和参比制剂的主要药动学参数为:Cmax为(202±107)和(218±109)μg/L;tmax为(4.2±0.8)和(3.9±0.8)h;AUC0-t为(2494±1163)和(2657±1424)μg.h.L-1;AUC0-∞为(2705±1290)和(2870±1578)μg.h.L-1;AUC0-t/AUC0-∞为(92.3±5.2)和(93.6±4.1)%;t1/2为(19.3±5.5)和(18.0±5.1)h。餐后给药试验制剂的相对生物利用度F为(100.5±33.1)%。结论:两种制剂在空腹给药和餐后给药时都具有生物等效性。餐后给药组Cmax和AUC均明显高于空腹给药组,建议临床使用餐后服用药物,以提高药物的生物利用度,增强疗效。

AIM： To study the bioequivalence of domestic Itraconazole capsules in healthy Chinese volunteers before diet or after diet respectively.METHODS： There were two randomized,open-label,two-period clinical studies,and 24 healthy Chinese male volunteers were enrolled in each study.All the volunteers in each study had taken a single dose of 200 mg Itraconazole test capsules and 200 mg of its reference.The plasma Itraconazole concentration were determined by HPLC-MS/MS.The major harmacokinetic parameters were calculated,the bioequivalence of Itraconazole test capsule and its reference before diet as well as after diet were evaluated respectively.RESULTS：The pharmacokinetic parameters before diet were as follows： Cmax were（124±79） and（124±86） μg/L;tmax were（2.9±0.8） and（2.5±0.9） h;AUC0-t were（1320±826） and（1348±1095） μg·h·L-1;AUC0-∞ were（1420±902）and（1444±1148） μg·h·L-1;AUC0-t/AUC0-∞ were（93.0±4.9）% and（92.3±5.1）%;t1/2 were（17.7±4.7） and（18.1±2.8） h.The relative bioavailability of the test capsule was（106.5±35.4）%.The pharmacokinetic parameters after diet were as follows： Cmax were（202±107） and（218±109） μg/L;tmax were（4.2±0.8）and（3.9±0.8） h;AUC0-t were（2494±1163）and（2657±1424）μg·h·L-1;AUC0-∞ were（2705±1290） and（2870±1578） μg·h·L-1;AUC0-t/AUC0-∞ were（92.3±5.2）%/（93.6±4.1）%;t1/2 were（19.3±5.5） and（18.0±5.1） h.The relative bioavailability of the test capsule was（100.5±33.1） %.CONCLUSION： The Itraconazole test capsule and its reference were bioequivalent both when administrated before diet and after diet.The Cmax and AUC were both significant higher when administrated after diet,so it is better to dose after diet for Itraconazole capsule in order to gain a higher bioavailability and an increased effect.