Trausch B, Terhaag B, Gebhardt M, Richter K, Oertel R
Institute of Clinical Pharmacology, Medical Academy C.G. Carus, Dresden, Germany.
Int J Clin Pharmacol Ther Toxicol. 1992 Nov;30(11):508-9.
The biliary and renal elimination of the new muscarinic-1-antagonist AWD 26-06 were investigated in 6 female volunteers (age: 26-69 years) 9-14 days after cholecystectomy and T-tube construction. After a single oral dose of 50 mg AWD 26-06 as an aqueous solution the amount of the unchanged substance was determined in serum, T-tube bile and urine with a special HPLC-method. The concentration maximum was reached earlier and higher in bile (60 +/- 22 min; 10.8 +/- 5.7 micrograms/ml) than in serum (73 +/- 28 min; 0.98 +/- 0.53 micrograms/ml). During the whole observation time of 24 h the AWD 26-06 concentration in bile was 2-21-fold higher than in serum. In mean 2.3 +/- 1.5% of the administered dose were eliminated unchanged by bile and 12.2 +/- 5.9% by urine. More than 70% of the dose were metabolized. The results gave a hint at active liver transport processes and an enterohepatic recirculation. A drug interaction was observed with valproic acid on the metabolic level. The great interindividual variability of pharmacokinetic data can be caused by the heterogeneity of the subject group and a genetic polymorphism in the metabolism of AWD 26-06. The bile sampling by means of a T-tube is a simple but effective method under consideration of special conditions.
在6名女性志愿者（年龄：26 - 69岁）行胆囊切除术后9 - 14天且放置T管引流时，研究了新型毒蕈碱 - 1拮抗剂AWD 26 - 06的胆汁和肾脏排泄情况。单次口服50 mg AWD 26 - 06水溶液后，采用特殊的高效液相色谱法测定血清、T管胆汁和尿液中未变化物质的量。胆汁中浓度达到峰值的时间更早且更高（60±22分钟；10.8±5.7微克/毫升），高于血清（73±28分钟；0.98±0.53微克/毫升）。在24小时的整个观察期内，胆汁中AWD 26 - 06的浓度比血清高2 - 21倍。平均而言，给药剂量的2.3±1.5%通过胆汁以未变化形式排泄，12.2±5.9%通过尿液排泄。超过70%的剂量发生了代谢。结果提示存在活跃的肝脏转运过程和肠肝循环。在代谢水平上观察到与丙戊酸存在药物相互作用。药代动力学数据的个体间差异较大可能是由于受试者群体的异质性以及AWD 26 - 06代谢中的基因多态性所致。在考虑特殊条件下，通过T管进行胆汁采样是一种简单而有效的方法。
