Wahl D, van Wayjen R G, van den Ende A A
Arzneimittelforschung. 1985;35(1A):266-72.
The present paper reports on the human pharmacokinetics of (8r)-6 beta, 7 beta-epoxy-8-ethyl-3 alpha-/(-)-tropoyloxy/-1 alpha H, 5 alpha H-tropanium bromide (oxitropium bromide, Ba 253 BR, Ventilat) after intravenous and oral administration as well as following inhalation. The 14C-labelled substance was used. The concentrations of radioactivity measured in the plasma after i.v. administration show a biphasic course, a rapid alpha phase and a terminal phase (t 1/2 = 1.5 h). Once the alpha phase has passed the radioactivity concentrations measured after i.v. administration of 1 mg are comparable with those after 20 mg administered orally. The concentration course after inhalation corresponds essentially to the course after oral administration of lower doses. The cumulative renal excretion of the radioactivity is 68-78% for i.v. administration, 13% for oral administration, and 10% for inhalation. 7% (i.v.), 77% (p.o.) and 88% (inhalation) is excreted in the faeces. Oxitropium bromide is rapidly hydrolysed after oral administration. As little as 4 h later only 2-3% of intact active ingredient is found, whereas there is 85% of the hydrolysed product in the urine. A similar distribution pattern is observed in urine samples taken later. Some other metabolites are also recorded in minimal quantities. After i.v. administration, too, the hydrolysed product is excreted as the main component.
本文报道了（8r）-6β，7β-环氧-8-乙基-3α-（-）-托品酰氧基-1αH，5αH-托烷溴化物（氧托溴铵，Ba 253 BR，Ventilat）静脉内、口服及吸入给药后的人体药代动力学。使用了14C标记的物质。静脉内给药后血浆中测得的放射性浓度呈双相过程，即快速的α相和终末相（t 1/2 = 1.5小时）。一旦α相过去，静脉内给予1mg后测得的放射性浓度与口服20mg后测得的浓度相当。吸入后的浓度过程基本上与口服较低剂量后的过程一致。放射性的累积肾排泄量静脉内给药为68 - 78%，口服给药为13%，吸入给药为10%。7%（静脉内）、77%（口服）和88%（吸入）经粪便排泄。氧托溴铵口服后迅速水解。仅4小时后，完整活性成分仅发现2 - 3%，而尿液中有85%的水解产物。在随后采集的尿液样本中观察到类似的分布模式。还记录到少量其他代谢产物。静脉内给药后，水解产物也是主要的排泄成分。
