Comparison of the effects of percutaneous and intraduodenal administration of oxybutynin on bladder contraction and salivation in rabbits

Abstract

Aim: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. Conclusion: 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.

Electron capture detection of oxybutynin in plasma: precolumn derivatization approach and application to a pharmacokinetic study

“…The limit of detection (LOD) of the developed method was found to be 0.1 ng ml À1 (calculated with reference to the formula and guidelines provided by the United States Food and Drug Administration as well as by the European Medicines Agency). 25,26 This value was found to be signicantly lower than the previously reported values for the bioanalytical methods of Mizushima et al 27,28 (2 ng ml À1 and 0.51 ng ml À1 ), Zobrist et al 29 (0.5 ng ml À1 ), and Kontani et al 12 (0.5 ng ml À1 ). The results obtained were veried by GC-MS analysis of the derivative.…”

“…Hence, it is necessary to use the other physicochemical properties of oxybutynin and advanced instrumentation, such as hyphenated techniques like GC-MS [9][10][11] or LC-MS, for detection purposes. [12][13][14][15][16] Typically, GC is used to analyze volatile substances. GC not only eliminates the use of the photochemical detection of analytes but also the use of solvents interfering in photochemical detection.…”

Limitations in using rabbit bladders in electrophysiological and urodynamic experiments

“…There are no data in the available literature of comparable experiments concerning these animals. Pharmacologically modified P ves values in rabbits have been described to reach up to 20 cm H 2 O (Kontani et al 2006;Chou et al 2007), although no parameter for comparison at different bladder filling densities is described. Lin (Lin et al 2005) also described P ves values of under 20 cm H 2 O for rabbits in a study of the influence of ischaemia on the bladder, although the study focused on pressure in overfilled bladders achieved under entirely different circumstances.…”

“…The urinary bladder volume was chosen partly based on the determined mean amount of natural content and partly based on data in the literature (Kontani et al 2006;Chou et al 2007;Gomez et al 2011). No substance was used that could affect the muscle response during root stimulation.…”

Development of Supported Liquid-Phase Microextraction Probes for In Vivo PK Studies

“…Oxybutynin PKs has been studied before in both humans and rabbits (a well-accepted model for the corresponding human disease) [22][23][24][25]. However, the studies involved lengthy analytical procedures and only the plasma concentrations of oxybutynin were measured.…”