联苯双酯制剂生物利用度的研究

本文报道用高效液相色谱法测定联苯双酯制剂在动物及人体内的血药浓度。结果提示:滴丸的生物利用度较片剂等供试制剂明显提高,家兔口服后血药浓度一时间曲线下面积滴丸是片剂的13～19倍,在人体内则较片剂提高2倍左右,在家兔、大鼠及人体的粪便排泄亦明显低于片剂或淀粉悬液。对小鼠四氯化碳肝损伤预防作用所需联苯双酯的剂量。滴丸仅为悬液的七分之一。可见联苯双酯滴丸的生物利用度较其它制剂为高。

BIOAVAILABILITY STUDIES ON THE PREPARATIONS OF BIPHENYL DIMETHYL DICARBOXYLATE(DDB)

Since the bioavailability of the suspension and the tablet of DDB given orally is only 20-30%, we have prepared four kinds of DDB solid dispersion preparations (DDB pilule I with polyethylene glycol 6000 as the vehicle, DDB pilule II with polyethylene glycol 6000 and absorption accelerator as the vehicle, capsule of DDB-urea fusing mixture and DDB-polyvinyl pyrrolidone coprecipitate), and the bioavailability of these preparations were studied in rabbits, rats and human volunteers by HPLC method. All four preparations showed better absorption than the DDB tablet, and the area under serum DDB concentration-time curve of pilule II was 19 fold that of the tablet in rabbits, meaning that the absorption of pilule II is the best of the four preparations. After administration of the four solid dispersion preparations, the fecal excretion of DDB were all lower than the tablet in both animals and human volunteers. The protective action of pilule II against CCl4 hepatotoxicity was about six times stronger than that of the suspensions. Therefore, there are good reasons to use DDB pilule II instead of the tablets of suspension in the clinic.