尼美舒利栓药代动力学及相对生物利用度研究

目的　以市售的尼美舒利普通片为参比制剂 ,评价自制尼美舒利直肠栓的生物利用度和生物等效性。方法　采用随机交叉分组实验设计 ,5只新西兰家兔分别给予剂量 5 0 mg.kg- 1 的尼美舒利栓和普通片剂 ,栓剂直肠给药 ,片剂口服 ;按设计采集 2 4h内动态血标本 ;以 HPLC法测定血浆药物浓度 ;以二室模型计算两种制剂在动物体内的药动学参数和相对生物利用度。结果　参比制剂和受试制剂的 Tmax 分别为 ( 6.96± 1 .69) h和( 2 .0 3± 1 .0 7) h,Cmax 分别为 ( 65 .5 1± 2 8.0 9) mg.L- 1和 ( 65 .99± 1 2 .1 3 ) mg.L- 1 ,AUC0 - inf 分别为 ( 5 1 9.3 4±1 5 1 .0 5 ) mg.h.L- 1和 ( 4 40 .1 2± 72 .89) mg.h.L- 1 ,t1 / 2α分别为 ( 0 .63± 0 .1 3 ) h和 ( 2 .2 9± 0 .82 ) h,t1 / 2β分别为( 1 .72± 0 .95 ) h和 ( 1 .76± 0 .2 1 ) h,MRT分别为 ( 9.0 0± 1 .1 6) h和 ( 6.2 4± 0 .62 ) h,滞后时间分别为 ( 5 .42±1 .63 ) h和 ( 0 .0 7± 0 .0 9) h,以市售 NIM普通片为参比制剂 ,NIM直肠栓的相对生物利用度为 84.75 %。结论　统计结果显示 ,各主要药动学参数均有显著性差异。尼美舒利栓具有明显的速释特征 ,与尼美舒利普通片生物不等效。

Study on pharmacokinetics and relative bioavailability of nimesulide suppositories

Objective To study the relative bioavailability and bioequivalence of nimesulide suppositories in New Zealand rabbits.Methods A rapid and sensitive HPLC method was applied for the determination of the drug levels in plasma.In a randomized two way crossover design, the drugs were administrated by rectal and gastric,respectively in 50 mg·kg -1 single dose,to 5 male New Zealand rabbits.The parameters were estimated by two compartment model with a statistic analysis of PEMs.Results The T max ,C max ,AUC 0 inf ,t 1/2α ,t 1/2β ,MRT,lag time of nimesulide common tablets and suppositories were(6 96±1 69)h and (2 03±1 07)h,(65 51±28 09)mg·L -1 and (65 99±12 13) mg·L -1 , (519 34±151 05) mg·h·L -1 and (440 12±72 89) mg·h·L -1 ,0 63±0 13)h and(2 29±0 82)h,(1 72±0 95)h and(1 76±0 21)h, 9 00±1 16)h and(6 24±0 62)h,(5 42±1 63)h and(0 07±0 09)h,respectively.The mean relative bioavailability of the nimesulide suppositories vs common tablets was 84 75%.Conclution The results suggested that the two formulations were not bioequivalent and the nimesulide suppositories realeased more quickly than common tablets did.