Pharmacokinetics and tissue distribution of the anticholinergics tiotropium and ipratropium in the rat and dog

Biopharm Drug Dispos. 2001 Jul;22(5):199-212. doi: 10.1002/bdd.280.


Ipratropium, a current treatment for chronic obstructive pulmonary disease (COPD) and tiotropium, a longer acting anticholinergic bronchodilator currently being developed for COPD are structurally related to atropine. In this study, the intravenous (i.v.), oral (p.o.) and intratracheal ( single dose pharmacokinetics (PK) of tiotropium and ipratropium were determined in rat and dog. In rats, concentration-time profiles of tiotropium and ipratropium after single i.v. bolus administration of 7-8 mg kg(-1) are similar. Both drugs are highly cleared (Cl between 87 and 150 ml min(-1) kg(-1)) and extensively distributed into tissues (volume of distribution V(ss) between 3 and 15 l kg(-1)). In dogs, this holds also true for both drugs (Cl between 34 and 42 ml min(-1) kg(-1), V(ss) between 2 and 10 l kg(-1)), although different dose regimen were applied (i.v. bolus of 0.08 mg kg(-1) vs. infusion of 0.1 mg kg(-1) h(-1) for 3 h). Tiotropium plasma concentrations increased linearly in rats over a wide dose range following single i.v. administration. Both ipratropium and tiotropium showed a comparable terminal elimination half-life in rat urine (21-24 h) after single i.v. administration, which was much longer than the corresponding half-life in plasma (6-8 h). Whole body autoradiography in rats revealed a broad and rapid tissue distribution of [(14)C]tiotropium radioactivity after single i.v. administration. A comparable distribution pattern has also been reported earlier for ipratropium.

MeSH terms

  • Animals
  • Cholinergic Antagonists / pharmacokinetics*
  • Dogs
  • Female
  • Ipratropium / administration & dosage
  • Ipratropium / pharmacokinetics*
  • Male
  • Rats
  • Rats, Wistar
  • Scopolamine Derivatives / administration & dosage
  • Scopolamine Derivatives / pharmacokinetics*
  • Tiotropium Bromide
  • Tissue Distribution


  • Cholinergic Antagonists
  • Scopolamine Derivatives
  • Ipratropium
  • Tiotropium Bromide