Verhagen M A, Samsom M, Maes B, Geypens B J, Ghoos Y F, Smout A J
Department of Gastroenterology, University Hospital, Utrecht, The Netherlands.
Aliment Pharmacol Ther. 1997 Dec;11(6):1077-86. doi: 10.1046/j.1365-2036.1997.00260.x.
ABT-229 is a recently developed derivative of erythromycin, devoid of antibiotic activity. We studied the effect of ABT-229 on gastric emptying and postprandial antroduodenal motility in healthy volunteers.
Placebo, 4 and 16 mg ABT-229 were given as a single oral dose to nine healthy volunteers, in a randomized, 3-period crossover design. A solid meal (250 kcal) was given twice, 45 min after drug ingestion and 4 h later. Gastric emptying of each meal was studied using the 13C-octanoic breath test. Antroduodenal motility was recorded during the total 9-h period.
After the first meal, both the 4 and 16 mg doses increased the gastric emptying rate to a similar extent. ABT-229 stimulated the contractile motility of the antrum dose-dependently. The half-emptying time and the lag-phase of gastric emptying correlated with the number of pressure waves that were propagated over the antrum and the mean amplitude of antral pressure waves. After the second meal no significant effects of ABT-229 were found.
A single dose of the new motilin agonist ABT-229 strongly increases the gastric emptying rate in healthy volunteers by increasing the strength and length of propagation of antral pressure waves. ABT-229 has the potential to become a new prokinetic drug.
ABT - 229是一种最近研发的红霉素衍生物,无抗生素活性。我们研究了ABT - 229对健康志愿者胃排空及餐后胃十二指肠运动的影响。
采用随机、3期交叉设计,给9名健康志愿者单次口服安慰剂、4毫克和16毫克ABT - 229。服药后45分钟和4小时分别给予一次固体餐(250千卡)。采用13C - 辛酸呼气试验研究每餐的胃排空情况。在整个9小时期间记录胃十二指肠运动。
第一餐后,4毫克和16毫克剂量均使胃排空率增加到相似程度。ABT - 229剂量依赖性地刺激胃窦的收缩运动。胃排空的半排空时间和延迟期与通过胃窦传播的压力波数量及胃窦压力波的平均幅度相关。第二餐后未发现ABT - 229有显著影响。
单次服用新型胃动素激动剂ABT - 229可通过增加胃窦压力波的强度和传播长度,显著提高健康志愿者的胃排空率。ABT - 229有潜力成为一种新型促动力药物。