妥洛特罗贴片人体药物动力学研究

Pharmacokinetics of Tulobuterol Patches in Human

采用单剂量给药、双周期交叉设计,在8名男性健康志愿者中比较给予妥洛特罗(1)贴片2mg和口服1片0．862mg的药物动力学特点。采用LC-MS／MS法测定血浆中1的浓度。志愿者单次使用1贴片2mg的主要药物动力学参数分别为:Cmax(1．13±0．40)ng／ml,tmax(9．50±2．07)h,t1／2(9．72±2．78)h,MRT(22．74±5．20)h,AUC0→t(18．65±6．92)ng·ml-1·h,进入体内药量为(0．193±0．072)mg。经剂量校正,贴片相对于口服片剂的平均生物利用度为(81．05±27．91)％。说明1贴片透皮吸收良好,与口服1片相比,峰浓度降低、达峰时间和MRT显著延长,具有缓释的释药特征。

According to a randomized two-period crossover design, 8 male health volunteers were pasted with 2mg tulobuterol patches and orally administrated with 0.862mg conventional tulobuterol tablets, respectively, with a 7-day washout. The plasma concentration of tulobuterol was determined by a validated LC-MS/MS method. The main pharmacoldnetic parameters of tulobuterol patches were Cmax （1.13 ± 0.40） ng/ml, tmax （9.50 ± 2.07） h, t1/2 （9.72 ± 2.78） h, MRT （22.74 ± 5.20） h, AUC0→t, （18.65 ± 6.92） ng·ml^ -1·h, and the quantity to be absorbed was （0.193 ± 0.072） mg. The mean relative bioavailability of tulobuterol patches was （81.05 ± 27.91） % as compared with conventional tablets after dose adjustment. The results, contrasted with oral administration, indicated that the patches were well absorbed with lower Cmax, and significantly longer tmax and MRT. The tulobuterol patches possessed the characteristic of sustained release.