微粉化马来酸多潘立酮在犬体内的绝对生物利用度研究

Studies on Absolute Bioavailability of Micronized Domperidone Maleate in Dogs

目的:研究微粉化的马来酸多潘立酮在犬体内的药动学及绝对生物利用度。方法:Beagle犬6只,随机分为2组,采用单剂量交叉给药方案,分别先后给予单剂量口服微粉化马来酸多潘立酮薄膜衣片和静脉注射微粉化马来酸多潘立酮,用HPLCFID法测定血药浓度,并用3p97程序拟合药动学参数。结果:微粉化马来酸多潘立酮在犬体内的药-时数据符合二室模型,主要药动学参数为:t1/2β=14.22min,CL=16.84mL/(h·kg),Cmax=25.47μg/L,tmax=34.23min,AUC0→∞=328129μg/(L·min)。此测定方法准确度高,灵敏,简便易行。微粉化后的马来酸多潘立酮的绝对生物利用度为40.43%。结论:微粉化后的马来酸多潘立酮的生物利用度较多潘立酮的生物利用度有所提高。

Objective： To evaluate pharmacokinetics and absolute bioavailability of micronized domperidone male.ate. Methods： A paired, crossover design was used. 12 dogs were randomly divided into two groups. Group one received the micronized domperidone maleate injection and followed by the membrane tablet and another group was given the membrane tablet and then the injection. Blood samples of two groups were collected at different time spots. Plasma concentration of domperidone male.ate was measured by HPLC-FID. The pharmacokinetie parameters were measured by 3p97 program and the absolute bioavailability was calculated. Results： The time-concentration relatiomhip of micronized domperidone maleate in dogs conforms to two compartment model. The major pharmacokinetic parameters of the injection were as follows： t1/2β = 14.22 rain, CL = 16.84 mL/（h · kg）, Cmax = 25.47 μg/L, tmax = 34.23 min and AUC0→∞ = 328 129 μg/（L·min）. This analytical method is accurate and sensitive. The absolute bioavailability of mieronized dompefidone male.ate is 40.43%. Conclusions： The absolute bioavailability of micronized domperidone maleate might be better than that of the general domperidone.