Müller C, Siegmund W, Huupponen R, Kaila T, Franke G, Iisalo E, Zschiesche M
University of Greifswald, Medical Faculty, Department of Clinical Pharmacology, Germany.
Eur J Drug Metab Pharmacokinet. 1993 Jul-Sep;18(3):265-72. doi: 10.1007/BF03188807.
A pharmacokinetic study with 30 mg propiverine p.o. was performed in healthy volunteers (10 males, 6 females, age 36-56 years, body weight 55-100 kg, body height 162-184 cm, Broca index 0.96-1.19). 8 of them were poor and 8 extensive metabolizers of the debrisoquine type hydroxylation polymorphism. The total anticholinergic activity of the parent compound and active metabolites was measured with a radioreceptor assay calibrated with the metabolite M2. The affinity of this metabolite to the muscarinic receptors was similar to that of atropine. The urinary excretion of 3 major metabolites was determined with TLC and densitometry. Arterial blood pressure, heart rate, diameter of pupils, accommodation and parotic salivary flow were also measured. The concentrations of anticholinergic equivalents of propiverine were below 1 ng/ml of M2. 1.4-6.0% of the dose were excreted as N-oxidized metabolites into the urine. The poor and extensive metabolizers of debrisoquine did not differ significantly with regard to the concentration time behaviour of the active drug components, pattern of major metabolites, adverse drug reactions or any pharmacodynamic parameters measured.
在健康志愿者（10名男性，6名女性，年龄36 - 56岁，体重55 - 100 kg，身高162 - 184 cm，布罗卡指数0.96 - 1.19）中进行了一项口服30 mg丙哌维林的药代动力学研究。其中8人是异喹胍型羟基化多态性的慢代谢者，8人是快代谢者。用经代谢物M2校准的放射受体分析法测定母体化合物和活性代谢物的总抗胆碱能活性。该代谢物对毒蕈碱受体的亲和力与阿托品相似。用薄层色谱法和密度测定法测定3种主要代谢物的尿排泄量。还测量了动脉血压、心率、瞳孔直径、调节功能和腮腺唾液流量。丙哌维林的抗胆碱能等效物浓度低于1 ng/ml的M2。1.4 - 6.0%的剂量以N - 氧化代谢物的形式排泄到尿液中。异喹胍的慢代谢者和快代谢者在活性药物成分的浓度 - 时间行为、主要代谢物模式、药物不良反应或任何测量的药效学参数方面没有显著差异。
