[논문]Absorption of oxybutynin from vaginal inserts: drug blood levels and the response of the rabbit bladder

doi:10.1016/S0090-4295(00)00782-2

[해외논문] Absorption of oxybutynin from vaginal inserts: drug blood levels and the response of the rabbit bladder

Urology, v.56 no.6, 2000년, pp.1063 - 1067

Schröder, Annette (Department of Urology, Johannes Gutenberg-University, Mainz, Germany) , Levin, Robert M (Albany Medical College, Albany, New York, USA) , Kogan, Barry A (Albany Medical College, Albany, New York, USA) , Das, Anurag K (Albany Medical College, Albany, New York, USA) , Kay, Francine (FEI Enterprises Ltd, Plainsboro, New Jersey, USA) , Mahashabde, Anu (FEI Enterprises Ltd, Plainsboro, New Jersey, USA)

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AbstractObjectives. Oxybutynin has been used for treatment of urge urinary incontinence for more than 20 years. However, one of the major problems with its use is uncomfortable anticholinergic side effects that can lead to discontinuation of treatment. Alternative forms of drug administration may reduce side effects and thus improve patient compliance.Methods. A cylinder-shaped, curved silicone elastomer insert containing oxybutynin was anchored in the vagina of female rabbits. The inserts were designed to release oxybutynin at rates of 0.5, 1.0, and 5.0 mg/day, respectively. Blood drug and metabolite levels were monitored for 1 to 7 days and cystometry was carried out after 7 days of treatment.Results. There was a consistent dose-dependent absorption of the oxybutynin resulting in stable plasma concentrations by 3 days. Levels of N-desethyloxybutynin, the active metabolite that is thought to be responsible for side effects, were less than 1.0 ng/mL in all groups. The cystometrograms showed a decrease in the detrusor pressures for the higher oxybutynin groups and a dose-dependent decrease in micturition pressure. The vaginal wall in contact with the insert showed no irritation.Conclusions. The inserts produced stable blood levels and released sufficient amounts of oxybutynin to have measurable effects on the bladder. There was no irritating effect of the insert on the vaginal wall after a 1-week treatment. Vaginal inserts containing oxybutynin may be an interesting alternative method for the chronic delivery of oxybutynin.

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DOI : 10.1016/S0090-4295(00)00782-2
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