title: Comparison of the effects of percutaneous and intraduodenal administration of oxybutynin on bladder contraction and salivation in rabbits.
abstract: OBJECTIVE
  As only a few basic animal experiments have assessed the usefulness of percutaneous application of oxybutynin, we compared the effects of percutaneous application and intraduodenal injection of oxybutynin on urinary bladder contraction accompanied by micturition in conscious rabbits and salivation in anesthetized rabbits.
  
  
  METHODS
  Bladder contractions were induced by continuous infusion of saline (2 mL/min) into the bladder. Salivary secretion was induced by pilocarpine (0.1 mg/kg, i.v.). Oxybutynin was administered at 15 mg/animal, and the plasma concentrations of oxybutynin and N-desethyloxybutynin were measured by high-performance liquid chromatography to clarify the effective concentration.
  
  
  RESULTS
  The intercontraction interval (ICI) was prolonged from 0.5 h after intraduodenal injection of oxybutynin, and this effect continued for 2 h. The ICI prolongation after percutaneous application of oxybutynin appeared at 2 h and continued throughout the 6-h experimental period. The saliva secretion induced by pilocarpine was inhibited to almost the same level by oxybutynin 3 h after intraduodenal injection and 6 h after percutaneous application. However, the sum of the plasma concentrations of oxybutynin and N-desethyloxybutynin rose steeply to a very high level within 20 min after oral administration instead of intraduodenal injection and decreased within 3 h to about half of the level evident 6 h after percutaneous application.
  
  
  CONCLUSIONS
  We confirmed that percutaneous application of oxybutynin caused long-lasting ICI prolongation in our rabbit model, as compared with that after intraduodenal injection, and produced weaker inhibitory effects on saliva secretion because it did not cause steep elevation of the plasma concentration.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan. h-kontani@hokuriku-u.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kontani
authors.forename: Tetsukazu
authors.initials: T
authors.lastname: Hamamoto
authors.forename: Sunao
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Yukari
authors.initials: Y
authors.lastname: Nomura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sawanishi
authors.forename: Haruo
authors.initials: H
authors.lastname: Saito
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D004386:Duodenum; D007267:Injections; D008297:Male; D008333:Mandelic Acids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009119:Muscle Contraction / Q000187:drug effects*; D010276:Parasympatholytics / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011817:Rabbits; D012472:Salivation / Q000187:drug effects*; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
chemical_list: D008333:Mandelic Acids; D010276:Parasympatholytics; C005419:oxybutynin