Lutz D, Gielsdorf W, Rasper J, Jaeger H, Albring M, Eisler G, Niebch G
Arzneimittelforschung. 1985;35(1):163-6.
The relative bioavailabilities and pharmacokinetic profiles of 2 carbocisteine preparations (capsules, granulate) were evaluated in a single dose and a steady state study. 10 healthy volunteers took in a randomized, 2fold cross over design 750 mg 3-(carboxymethylthio)alanine (carbocisteine, Transbronchin) (1 portion of the granulate or 2 capsules) as a single dose or for 4 days 3 times a day (every 8 h) 1 portion of the granulate or 2 capsules, respectively. During the saturation phase the pre-dose serum levels in the morning were determined and on day 5 - after a last dosing the elimination kinetics were evaluated. The same time frame of blood withdrawals was used for the evaluation of serum kinetics after single dosing. The new developed gaschromatographic method for the rapid, sensitive and reliable quantitative determination of carbocisteine in serum saves not only a lot of time but also improves the detection limit and selectivity by a factor of approx. 10. The studies revealed bioequivalency of the carbocisteine granulate and capsule preparations. After multiple dosing, no cumulation of the carbocisteine serum levels occurred. A comparison of the AUCo-infinity and AUC tau (single/multiple dosing, respectively) showed linear pharmacokinetics without enzyme induction or saturation phenomena in man.
在单剂量和稳态研究中评估了2种羧甲司坦制剂（胶囊、颗粒剂）的相对生物利用度和药代动力学特征。10名健康志愿者按照随机、双交叉设计，单剂量服用750 mg 3-（羧甲基硫代）丙氨酸（羧甲司坦，易咳净）（1份颗粒剂或2粒胶囊），或分别每天3次（每8小时1次）服用1份颗粒剂或2粒胶囊，持续4天。在饱和阶段，测定早晨给药前的血清水平，并在第5天——末次给药后评估消除动力学。单剂量给药后血清动力学评估采用相同的采血时间框架。新开发的气相色谱法用于快速、灵敏且可靠地定量测定血清中的羧甲司坦，不仅节省了大量时间，还将检测限和选择性提高了约10倍。研究表明羧甲司坦颗粒剂和胶囊制剂具有生物等效性。多次给药后，羧甲司坦血清水平未出现蓄积。对AUC0至无穷大以及AUCτ（分别为单剂量/多剂量给药）的比较显示，人体药代动力学呈线性，无酶诱导或饱和现象。
