摘要
目的 研究普罗布考包合物胶囊在家犬体内的药代动力学与相对生物利用度。方法 用高效液相色谱法测定 6条健康犬po 2 5 0mg普罗布考片 (制剂A)或普罗布考包合物胶囊 (制剂B)后不同时间血浆中活性药物的浓度 ,绘制药 时曲线 ,计算药代动力学参数及相对生物利用度。结果 制剂A和制剂B的药 时曲线符合二室模型 ,其Tmax均为 (9 3± 2 1)h ,Cmax分别为 (1 5± 1 0 ) μg·mL- 1 和 (2 3± 0 9) μg·mL- 1 ,AUC0～ 2 40 分别为 (85± 5 6 ) μg·h·mL- 1 和(134± 5 5 ) μg·h·mL- 1 。以制剂A为参比 ,制剂B中普罗布考的相对生物利用度为 (198± 90 ) % ,两种制剂的AUC0～ 2 40有显著性差异 (P <0 0 5 )。结论 初步分析认为 ,改善普罗布考的水溶性是提高普罗布考生物利用度的关键因素之一。
AIM To study the pharmacokinetics and relative bioavailability of probucol inclusion complex capsule. METHODS Following oral administration of a single dose of 250 mg of conventional tablet (formulation A, purchased from the market) and probucol inclusion complex capsule (formulation B, a new formulation for preclinical trial) to each of 6 healthy dogs in a randomized crossover design, the plasma levels of the active drug at different time points were determined by HPLC and the plasma concentration-time profiles of formulation A and B were obtained. The pharmacokinetic parameters as well as relative bioavailability were analyzed. RESULTS The concentration-time curves of formulation A and formulation B were found to fit a two-compartment open model. The T max values of formulation A and formulation B were (9 3±2 1) h and (9 3±2 1) h, the C max values were (1 5±1 0) μg·mL -1 and (2 3±0 9) μg·mL -1 and the AUC 0～240 values were (85±56) μg·h·mL -1 and (134±55) μg·h·mL -1 , respectively. The relative bioavailability of formulation B was found to be (198±90)% compared with formulation A. The results of variance analysis and two one-side t -test showed that there was significant difference between the two formulations in the AUC 0～240 . CONCLUSION The high bioavailability by the inclusion of formulation B is attributed to the improvement of its water-solubility by the inclusion process and this is supposed to be a key factor for improving drug bioavailability.
出处
《药学学报》
CAS
CSCD
北大核心
2002年第3期210-213,共4页
Acta Pharmaceutica Sinica
