Appell Rodney A, Chancellor Michael B, Zobrist R Howard, Thomas Heather, Sanders Steven W
Department of Urology, Baylor College of Medicine, Houston, Tex 77030, USA.
Mayo Clin Proc. 2003 Jun;78(6):696-702. doi: 10.4065/78.6.696.
To compare the pharmacokinetics and adverse effect dynamics of 2 modified-release oxybutynin treatments.
Between October 15 and November 6, 2001, 13 healthy subjects (7 men and 6 women) participated in a randomized, 2-way crossover study of transdermal (Oxytrol, 3.9 mg/d) and extended-release oral (Ditropan XL, 10 mg) oxybutynin. Multiple blood and saliva samples were collected. Pharmacokinetic parameters and total salivary output were assessed. Statistical analyses included 95% confidence intervals, paired t test, analysis of variance, and linear regression.
Steady-state plasma concentrations were achieved after the first transdermal application and after the second extended-release oral dose. Mean +/- SD 24-hour oxybutynin areas under the concentration-time curve were comparable during transdermal and oral extended-release treatments, 10.8 +/- 24 vs 9.2 +/- 33 ng x h(-1) x mL(-1), respectively. However, the ratio of area under the curve (N-desethyloxybutynin/oxybutynin) after transdermal administration (1.2 +/- 03) was significantly lower (P < .001) than after extended-release oral administration (4.1 +/- 0.9). Mean plasma concentrations were less variable during transdermal compared with extended-release oral administration. Mean +/- SD saliva output was greater during transdermal than extended-release oral treatment (15.7 +/- 93 vs 12.2 +/- 6.8 g, respectively; P = .02). Lower N-desethyloxybutynin during transdermal application was associated with greater saliva output (r = -059, P = .04). No clinically important treatment-related adverse effects were observed.
Transdermal oxybutynin administration results in greater systemic availability and minimizes metabolism to N-desethyloxybutynin compared with extended-release oral administration. Lower N-desethyloxybutynin plasma concentration and greater saliva output during transdermal treatment correspond to the reported low incidence of dry mouth in patients with overactive bladder.
比较两种改良释放型奥昔布宁治疗的药代动力学和不良反应动态变化。
2001年10月15日至11月6日期间，13名健康受试者（7名男性和6名女性）参与了一项关于经皮（奥昔布宁贴片，3.9毫克/天）和缓释口服（得妥长效片，10毫克）奥昔布宁的随机、双向交叉研究。采集了多份血液和唾液样本。评估了药代动力学参数和唾液总分泌量。统计分析包括95%置信区间、配对t检验、方差分析和线性回归。
首次经皮给药后和第二次缓释口服给药后均达到稳态血浆浓度。经皮和口服缓释治疗期间，奥昔布宁浓度-时间曲线下的平均±标准差24小时面积相当，分别为10.8±24与9.2±33纳克·小时⁻¹·毫升⁻¹。然而，经皮给药后曲线下面积（N-去乙基奥昔布宁/奥昔布宁）的比值（1.2±0.3）显著低于（P<.001）缓释口服给药后（4.1±0.9）。与缓释口服给药相比，经皮给药期间平均血浆浓度的变异性较小。经皮治疗期间的平均±标准差唾液分泌量大于缓释口服治疗（分别为15.7±9.3与12.2±6.8克；P=.02）。经皮给药期间较低的N-去乙基奥昔布宁与较多的唾液分泌量相关（r=-0.59，P=.04）。未观察到与治疗相关的具有临床重要意义的不良反应。
与缓释口服给药相比，经皮给予奥昔布宁可导致更高的全身可用性，并使代谢为N-去乙基奥昔布宁的过程降至最低。经皮治疗期间较低的N-去乙基奥昔布宁血浆浓度和较多的唾液分泌量与膀胱过度活动症患者中报道的口干低发生率相符。
