[Studies on pharmacokinetics and biotransformation of ipratropiumbromide in man (author's transl)]

Studies into the human pharmacokinetics of (8r)-3alpha-hydroxy-8-isopropyl-1 alphaH, 5 alphaH-tropanium-bromide- (+/-)-tropate (ipratropium bromide, Sch 1000, Atrovent) following inhalation and oral and i.v. administration are described. The substance was labelled with 14C. The plasma level (total radioactivity) recorded following oral administration was characterised by a low but broad plateau persisting for several hours. After i.v. injection rapid elimination from the plasma was observed in the first phase. The plasma level following inhalation was characterised by an initially rapid absorption and the curve subsequently resembled that following oral administration. An equi-bronchodilatory dose following inhalation produced a blood level 1000 times lower than those following oral dosing. The half-life of elimination lay between 3.2 and 3.8 h for all routes of administration. The maxima were recorded at 3 h. Cumulative renal excretion was 9.3% following oral administration, 72.1% following i.v. route and 3.2% after inhalation. 88.5% were excreted via the faeces following oral dosing, 6.3% following i.v. application and 69.4% after inhalation. Ipratropiumbromide is partly metabolised. After 4 h, the percentage of unchanged substance in relation to total activity in the urine was 24% (oral), 46% (i.v.) and 13% (inhalation). One of eight metabolites-- six in very small amounts-- was identified as N-isopropyl-methyl-nortropiumbromide.