吡罗昔康β-环糊精包合物的胃刺激性及生物利用度

STUDIES ON STOMACH IRRITATION AND BIOAVAILABILITY OF PIROXICAM β-CYCLODEXTRIN INCLUSION COMPOUND

本实验研究了吡罗昔康β-环糊精包合物对大鼠胃的刺激性,及其吡罗昔康β-环糊精包合物的胶囊的体外溶出速度和生物利用度。结果表明:吡罗昔康制成β-环糊精包合物后,刺激性远较吡罗昔康原料小。8名志愿者口服吡罗昔康β-环糊精包合物胶囊和吡罗昔康普通片后,用HPLC法测定血药浓度,经一室模型拟合,胺囊的AUC为片剂的110％,而吸收半衰期T_(1/2)(K_α)和达峰时T_m均小于片剂,这和体外溶出实验的结果,胶囊溶出速度显著大于片剂是相平行的。

The inclusion compound of piroxioam withβ-oyolodextrin (PIR/β-CD) wag studied in order to minimize the gastrointestinal irritation which is generally caused by piroxioam (PIR) itself. The suspensions of PIR/β-CD and intact PIR were administered into stomachs of both groups of seven Wistar male rate, and the degree of injury of stomach's, mucosa was observed by a dissection microscope, being eva-' luated by the six grades of numerical marks from 0 to 4.0., It was found that statistically significant difference batween the PIR/β-CD and intact PIR by t-test at 1% level, suggesting that the inclusion compound was very effective in reducing stomach injury.In a cross-over study, the bioavailability of PIR/β-OD in capsule form in 8 volunteers was compared with that of PIR conventional tablet by HPLC method. There were no significant difference in absorption extent of PIR between two dosage, forms, however, the T1/2(ka) and Tm of the capsule were smaller than that of tabled. This indicated that the PIR/β-OD would have somewhat quicker onset when compared with that of the tablet.This study showed that the PIR/β-CD was effective in reducing the injury of stomach upon oral administration, and in,addition to this it had a quicker onset in action. So that the PIR/β-CD might be a better dosage form in long-term oral therapy.