Sam Tasia S W, Cheng Jimmy T Y, Johnston Kevin D, Kan Kelvin K W, Ngan Man P, Rudd John A, Wai Man K, Yeung John H K
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR, China.
Eur J Pharmacol. 2003 Jul 4;472(1-2):135-45. doi: 10.1016/s0014-2999(03)01863-6.
Ondansetron (1-3 mg/kg), granisetron (0.3-1 mg/kg) and dexamethasone (0.3-1 mg/kg), administered at 12-h intervals, were investigated for their potential to prevent cisplatin (30 mg/kg, i.p.)-induced emesis during a 72-h observation period. Ondansetron appeared more active than granisetron to antagonise the emetic response occurring in the first 4-h (P<0.05) period, but none of the regimens significantly antagonised emesis during the 0-24- and 24-72-h periods (P>0.05). However, ondansetron was more active to antagonise emesis on day 1 using a more frequent drug administration, whereas bilateral vagotomy only reduced emesis for 2 h, and 5-HT, 2-methyl-5-HT and 1-m-chloro-phenylbiguanide (up to 20-30 mg/kg, i.p.) were not emetic. The combination of ondansetron 1 mg/kg and dexamethasone 1 mg/kg, both administered every 12 h, significantly delayed the onset of emesis (P<0.05) but failed to reduce the total numbers of retches+vomits over the 3-day period (P>0.05). Results are discussed in relation to the clinical situation.
在72小时观察期内，研究了以12小时间隔给药的昂丹司琼（1 - 3毫克/千克）、格拉司琼（0.3 - 1毫克/千克）和地塞米松（0.3 - 1毫克/千克）预防顺铂（30毫克/千克，腹腔注射）诱发呕吐的潜力。在最初4小时（P<0.05）内，昂丹司琼拮抗呕吐反应的活性似乎比格拉司琼更高，但在0 - 24小时和24 - 72小时期间，没有一种给药方案能显著拮抗呕吐（P>0.05）。然而，使用更频繁的给药方式时，昂丹司琼在第1天拮抗呕吐的活性更高，而双侧迷走神经切断术仅能减少2小时的呕吐，并且5 - HT、2 - 甲基 - 5 - HT和1 - 间氯苯双胍（腹腔注射剂量高达20 - 30毫克/千克）不会引起呕吐。每12小时给药一次的1毫克/千克昂丹司琼和1毫克/千克地塞米松联合使用，显著延迟了呕吐的发作（P<0.05），但在3天内未能减少干呕 + 呕吐的总数（P>0.05）。结合临床情况对结果进行了讨论。
