| Trimebutine maleate sustained-release pellet and metronidazole colon-specific pellet as new drug delivery systems were prepared in our laboratory. The propertis of these two preparations in vitro had already met with the requirements of initial design. In this study, the pharmacokinetics of these two preparations was investigated, and the correlation between the absorption in vivo and the release rate in vitro of these preparations was evaluated. The results would be instructional for the design of drugs and dosage forms, and offer some experimental evidences for reasonably use in clinic.The reverse-phase high performance liquid chromatography (RP-HPLC) and ultraviolet spectrophotometry (UV) methods were developed to determine the trimebutine maleate content and phenol red content, respectively. The linearity, specificity, repeatability and recovery met with the requirements of Chinese Pharmacopoeia (edition 2005). The absorption kinetics of trimebutine maleate in rats from different intestinal segments was studied by in situ recirculation The drug concentration in perfusate was determined by RP-HPLC. The research demonstrated that trimebutine maleate was mostly absorbed in duodenum, ileum and colon, the apparent absorption constants (ka) and absorption percentage (PA%) in duodenum,jejunum,ileum,colon were 0.2300±0.023,0.0838±0.051,0.2022±0.021,0.1669±0.038 (h-1), 44.76±5.027,14.48±4.15,42.80±3.27,40.21±4.59 (%) respectively; the intestinal absorptive extent of trimebutine maleate was not influenced by the excretion of bile; the intestinal absorption rate of trimebutine maleate followed first-order kinetics.Two RP-HPLC methods were developed to determine the trimebutine maleate content,metronidazole content in dog plasma, respectively. The linearity, specificity, repeatability and recovery met with the requirements of Chinese Pharmacopoeia (edition 2005). These two methods were used to study the pharmacokinetics of trimebutine maleate and metronidazole in dogs, respectively. The experimental data of drugs was analyzed by WinNonlin program and non-compartment model theory.Three dogs were orally treated with trimebutine maleate sustained-release pellet capsule (test),trimebutine maleate capsule (reference) of single dose, respectively. The plasma concentration-time curves of test and reference preparations of trimebutine maleate in dogs were described with one-compartment model. The Tmax (h),Cmax (ng·mL-1),t1/2 (h),AUC0-t (ng·h·mL-1),AUC0-∞(ng·h·mL-1) of test and reference preparations of trimebutine maleate were 2.05±0.24,211.9±7.5,1.58±1.43,357.5±25.8,382.62±32.6, 0.92±0.25,286.82±11.82,1.60±0.24,442.78±5.56,465.65±8.44, respectively. The relative bioavailability of trimebutine maleate sustained-release pellet capsules was 80.74±4.64 %, compared with trimebutine maleate capsules. Trimebutine maleate sustained-release pellet capsules were... |
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