Comparison of zafirlukast (Accolate®) absorption after oral and colonic administration in humans
Comparison of zafirlukast (Accolate®) absorption after oral and colonic administration in humans
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DOI：
10.1023/a:1007509112383
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发表时间：
2000-02-01
影响因子：
3.7
通讯作者：
Brouwer, KLR
中科院分区：
文献类型：
--
作者：
Fischer, JD;Song, MH;Brouwer, KLR
目的.本研究描述了扎鲁司特口服和结肠给药后的胃肠道（GI）吸收。5名健康受试者以随机交叉方式口服扎鲁司特溶液（40 mg）并通过口腔肠道管进入结肠。另外2例受试者接受了回肠远端给药。采集连续血样，用HPLC法测定血药浓度。口服与结肠给药后的平均rt SD药代动力学参数分别为：AUC（无穷大）分别为2076 +/- 548与602 +/- 373 ng*h/mL，C-max分别为697 +/- 314与194 +/- 316 ng/mL。平均结肠：口服AUC（无穷大）和C-max分别为0.29和0.30。经口和结肠给药后的中位t（max）值分别为2.0和1.35 h。一级吸收速率常数（K-a和K-ac）由一级消除的二室模型估计。K-AC：K-A是
Purpose. This study characterized the gastrointestinal (GI) absorption of zafirlukast after oral and colonic administration in humans.Methods. Five healthy subjects received zafirlukast solution (40 mg) orally and via an oroenteric tube into the colon in a randomized, crossover fashion. Two additional subjects were dosed into the distal ileum. Serial blood samples were obtained and plasma concentrations were quantitated by HPLC.Results. Mean rt SD pharmacokinetic parameters after oral vs. colonic administration were: AUC(infinity) of 2076 +/- 548 vs. 602 +/- 373 ng*h/mL, respectively, and C-max of 697 +/- 314 vs. 194 +/- 316 ng/mL, respectively. Mean colon:oral AUC(infinity) and C-max were 0.29 and 0.30, respectively. Median t(max) values were 2.0 and 1.35 hr after oral and colonic administration. First-order absorption rate constants (K-a and K-ac) were estimated from a two-compartment model with first-order elimination. K-ac:K-a was