高脂饮食对两种非诺贝特微粒化胶囊口服吸收的影响

Effect of Food on Relative Bioavailability of Fenofibrate Micronised Capsule

目的比较在空腹和高脂饮食下非诺贝特微粒化胶囊的生物等效性,了解食物对非诺贝特微粒化胶囊吸收的影响。方法分别在空腹或高脂饮食下,24名成年健康志愿者单剂量口服两种非诺贝特微粒化胶囊,用HPLC测定血药浓度,对其药动学参数进行统计分析。结果在空腹时,非诺贝特微粒化胶囊和力平之胶囊的主要药动学参数分别为AUC0→96:(208.4±65.0),(155.7±108.9)mg.h.L-1,ρmax:(10.1±3.0),(5.3±3.8)mg.L-1;tmax:(4.1±0.6),(6.0±2.6)h。在高脂饮食时,非诺贝特微粒化胶囊和力平之胶囊的主要药动学参数分别为AUC0→96:(221.7±57.6),(220.5±58.2)mg.h.L-1,ρmax:(14.2±2.5),(14.4±2.6)mg.L-1;tmax:(4.9±0.9),(4.5±1.1)h。经统计学分析,在空腹条件下非诺贝特微粒化胶囊与力平之胶囊生物不等效,前者的相对生物利用度以AUC0→96计为(153.2±40.0)%。而在高脂饮食下,非诺贝特微粒化胶囊与力平之胶囊生物等效,前者的相对生物利用度为(101.2±12.0)%。结论非诺贝特微粒化胶囊的生物利用度受高脂饮食影响不明显,但饮食可提高其ρmax,而高脂饮食可显著提高力平之胶囊的AUC和ρmax。

OBJECTIVE To investigate the effect of food on the relative bioavailability and pharmacokinetics of fenofibrate micronised capsule versus Lipanthyl capsule in healthy volunteers. METHODS Under fasting and high-fat breakfast fed condition,a single dose of 200 mg fenofibrate micronised capsule and Lipanthyl capsule was given to 24 healthy volunteers using an open-label ,randomized ,two-way crossover design. Fenofibric acid levels in plasma were determined by validated HPLC methods. RESULTS The pharmacokinetic parameters of fenofibrate micronised capsule and Lipanthyl capsule under fasting condition were as following： AUC0→96（208.4 ± 65.0） and （155.7 ± 108.9）mg·h · L^-1 ,ρmax（10. 1 ±3.0） and （5.33 ± 3. 8）mg · L^-1 tmax（4. 1±0.6） and （6. 0 ±2. 6）h,respectively. Then the main pharmacokinetic parameters of fenofibrate micronised capsule and Lipanthyl capsule under high-fat breakfast fed condi- tion were as follows AUG0→96 （221.7 ± 57. 6） and （220. 5 ± 58. 2） mg · h · L^-1 ,ρmax （14. 2 ±2. 5） and （14. 4 ± 2.6） mg · L^-1, tmax （4.9±0. 9） and （4. 5±1.1 ）h, respectively. The relative bioavailability of fenofibrate micronised capsule versus Lipanthyl capsule under fast condition was （ 153.2 ± 40. 0） % and was bioinequivelent. Then under high-fat breakfast fed condition, the relative bioavailability of fenofibrate micronised capsule versus Lipanthyl capsule was （ 101.2 ± 12. 0） % and was bioequivalent. CONCLUSION High-fat breakfast can little modify either the relative bioavailability or pharmacokinetic profile（ except ρmax） of fenofibrate micronised capsule, but the AUC and p of Lipanthyl capsule can be highly increased under high-fat breakfast fed condition.