Di Stasi S M, Giannantoni A, Vespasiani G, Navarra P, Capelli G, Massoud R, Stephen R L
Departments of Urology and Clinical Biochemistry, Tor Vergata University, Institutes of Pharmacology and Hygiene, Catholic University, Rome, Italy.
J Urol. 2001 Feb;165(2):491-8. doi: 10.1097/00005392-200102000-00032.
About 15% to 20% of patients with detrusor hyperreflexia do not benefit from oral oxybutynin regimens, frequently because of unpleasant side effects. Several reports indicate that intravesical oxybutynin is effective in many of these patients but there are some who still fail to respond.
A select group of 10 adults with detrusor hyperreflexia unresponsive to standard oral and intravesical oxybutynin regimens were treated at weekly intervals with 5 mg. oxybutynin orally, or 5 mg. oxybutynin in 100 ml. intravesically for 60 minutes of passive diffusion and for 30 minutes with 5 mA. electrical current. Each treatment (plus oral placebo and 2 intravesical controls) was associated with an 8-hour, full urodynamic monitoring session, and periodic blood and bladder content sampling.
There was no significant objective improvement with oral or intravesical passive diffusion oxybutynin. Conversely there was significant improvement in 5 of 6 objective urodynamic measurements with intravesical electromotive oxybutynin. Plasma profiles were a single peak and decay following oral oxybutynin and 2 distinct peaks with intravesical passive diffusion and electromotive oxybutynin. Area under the curve for intravesical passive diffusion were 709 ng. per 8 hours versus oral 1,485 (p <0.05) versus intravesical electromotive 2,781 (p <0.001). Bladder content samples confirmed oxybutynin absorption. Oral oxybutynin caused anticholinergic side effects in 7 of 10 patients. There were no side effects with intravesical passive diffusion or electromotive administrations.
Accelerated intravesical administration results in greater bioavailability and increased objective benefits without side effects in previously unresponsive patients compared with oral and intravesical passive diffusion oxybutynin administration.
约15%至20%的逼尿肌反射亢进患者无法从口服奥昔布宁治疗方案中获益，这通常是由于出现令人不适的副作用。多项报告表明，膀胱内灌注奥昔布宁对许多此类患者有效，但仍有一些患者无反应。
选取10名对标准口服和膀胱内灌注奥昔布宁治疗方案无反应的逼尿肌反射亢进成年患者，每周接受一次治疗，分别为口服5毫克奥昔布宁，或膀胱内灌注5毫克奥昔布宁（溶于100毫升溶液中，进行60分钟的被动扩散，并在5毫安电流下进行30分钟）。每次治疗（包括口服安慰剂和2次膀胱内对照）均伴有8小时的全面尿动力学监测，并定期采集血液和膀胱内容物样本。
口服或膀胱内被动扩散奥昔布宁后，客观上无显著改善。相反，膀胱内电动灌注奥昔布宁后，6项客观尿动力学测量中有5项有显著改善。口服奥昔布宁后血浆曲线为单峰并衰减，膀胱内被动扩散和电动灌注奥昔布宁后为2个明显的峰。膀胱内被动扩散的曲线下面积为每8小时709纳克，口服为1485纳克（p<0.05），膀胱内电动灌注为2781纳克（p<0.001）。膀胱内容物样本证实了奥昔布宁的吸收。10名患者中有7名口服奥昔布宁后出现抗胆碱能副作用。膀胱内被动扩散或电动灌注给药均无副作用。
与口服和膀胱内被动扩散奥昔布宁给药相比，加速膀胱内给药可提高生物利用度，并在先前无反应的患者中增加客观疗效且无副作用。
