School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
College of Pharmacy, Dongguk University-Seoul, Goyang, 10326, Republic of Korea.
Arch Pharm Res. 2017 Dec;40(12):1455-1463. doi: 10.1007/s12272-017-0988-9. Epub 2017 Nov 20.
Tolterodine, a nonselective muscarinic antagonist available only as immediate release (IR) or extended release (ER) oral formulations, is used for the treatment of overactive bladder (OAB). This study aimed to compare the efficacy and extent of dry mouth adverse effects of tolterodine transdermal patch to the oral formulation. The two formulations have been examined through the muscarinic receptor binding tests conducted in bladder and salivary gland tissues and the salivary secretion tests conducted in rats. Comparable average tolterodine blood concentration levels were obtained 3 h after oral administration of tolterodine 25 mg/kg and 12 h after transdermal application of tolterodine patch 6 mg/8 cm. While K in the bladder tissue increased to a similar degree in both formulations of tolterodine, K in the salivary gland increased to a greater degree in the oral formulation. These results indicate that similar degree of inhibitory effects were observed in the bladder for both formulations while less inhibitory effects were observed in the salivary gland with tolterodine transdermal formulation compared to the oral formulation. For assessment of salivary secretion, tolterodine transdermal patch 6 mg/8 cm application resulted in significantly less inhibitory effects than oral tolterodine 25 mg/kg. Therefore, this study suggests that tolterodine transdermal patch could be a useful formulation that provides uniform and consistent inhibitory effects to effectively control OAB symptoms with reduced severity of dry mouth in comparison to the oral formulation.
托特罗定是一种非选择性毒蕈碱拮抗剂，仅以速释（IR）或缓释（ER）口服制剂形式存在，用于治疗膀胱过度活动症（OAB）。本研究旨在比较托特罗定透皮贴剂与口服制剂治疗口干不良反应的疗效和程度。通过在膀胱和唾液腺组织中进行毒蕈碱受体结合试验以及在大鼠中进行唾液分泌试验来检查这两种制剂。口服托特罗定 25mg/kg 后 3 小时和透皮贴剂 6mg/8cm 后 12 小时，获得了可比的平均托特罗定血药浓度水平。虽然托特罗定两种制剂在膀胱组织中的 K 值增加到相似程度，但在唾液腺中的 K 值增加到更大程度。这些结果表明，两种制剂在膀胱中观察到相似程度的抑制作用，而与口服制剂相比，托特罗定透皮制剂在唾液腺中观察到的抑制作用较小。为了评估唾液分泌，托特罗定透皮贴剂 6mg/8cm 应用导致的抑制作用明显小于口服托特罗定 25mg/kg。因此，本研究表明，托特罗定透皮贴剂可能是一种有用的制剂，与口服制剂相比，它能提供均匀一致的抑制作用，有效控制 OAB 症状，同时减轻口干的严重程度。
