Bio-Images Research Ltd., Within Glasgow Royal Infirmary, 84 Castle Street, Glasgow G4 0SF, UK.
Int J Pharm. 2013 Sep 15;454(1):41-6. doi: 10.1016/j.ijpharm.2013.06.065. Epub 2013 Jul 5.
Conventional modified release preparations of tamsulosin HCl have been linked to increased incidence of cardiovascular adverse events, possibly due to rapid drug peaks soon after ingestion. A 'flattened' absorption profile has been shown to reduce the occurrence of these unwanted effects while improving symptom control. The potential of a novel triple-layered tablet to effect prolonged release and continuous absorption of tamsulosin HCl in the gastrointestinal tract was investigated in this clinical study. Gastrointestinal (GI) transit behaviour was monitored by scintigraphic imaging of technetium-labelled tablets. Drug absorption levels were simultaneously determined through pharmacokinetic analysis of blood samples. A mean Cmax of 6 ± 3 ng/nL was achieved after 324 ± 184 min (mean tmax). The mean AUC0-24 was noted as 4,359 ± 1,880 ng/mL min. The mean gastric emptying and colon arrival times of the tablets were 105.2 ± 68.9 and 270.1 ± 32.0 min post-dose; giving a mean small intestine transit time of 164.9 ± 83.6 min. Variations in gastrointestinal transit did not appear to influence drug absorption. Correlation of scintigraphic and PK data indicated that tamsulosin HCl is released steadily throughout the entire GI tract, suggesting that the mechanism of drug release is independent of GI site allowing drug release even in the low moisture environment of the colon.
盐酸坦索罗辛的常规改良释放制剂与心血管不良事件的发生率增加有关，这可能是由于摄入后药物迅速达到峰值。“平坦”的吸收曲线已被证明可降低这些不良作用的发生，同时改善症状控制。本临床研究旨在探究一种新型三层片剂在胃肠道中对盐酸坦索罗辛的延长释放和持续吸收的潜力。通过锝标记片剂的闪烁成像监测胃肠道（GI）转运行为。通过对血样的药代动力学分析同时确定药物吸收水平。在 324±184 分钟（平均 tmax）后，达到 6±3ng/nL 的平均 Cmax。平均 AUC0-24 为 4,359±1,880ng/mL min。片剂的平均胃排空和结肠到达时间为给药后 105.2±68.9 分钟和 270.1±32.0 分钟；小肠转运时间平均为 164.9±83.6 分钟。胃肠道转运的变化似乎并不影响药物吸收。闪烁成像和 PK 数据的相关性表明，盐酸坦索罗辛在整个胃肠道中稳定释放，这表明药物释放的机制独立于胃肠道部位，即使在结肠的低水分环境中也能释放药物。
