DO CONTINUOUS INFUSIONS OF OMEPRAZOLE AND RANITIDINE RETAIN THEIR EFFECT WITH PROLONGED DOSING
DO CONTINUOUS INFUSIONS OF OMEPRAZOLE AND RANITIDINE RETAIN THEIR EFFECT WITH PROLONGED DOSING
复制标题
DOI：
10.1016/s0016-5085(94)94341-9
复制
发表时间：
1994-01-01
期刊：
影响因子：
29.4
通讯作者：
WILDERSMITH, CH
中科院分区：
文献类型：
--
作者：
MERKI, HS;WILDERSMITH, CH
背景/目的长期输注H2-拮抗剂通常用于重症监护病房，尽管对超过最初24小时给药的抗分泌功效知之甚少。本研究的目的是评估的抗分泌作用的雷尼替丁和奥美拉唑的输液为72 hours.MethodsTwelve健康志愿者接受单独滴定72小时静脉输注奥美拉唑，雷尼替丁，或安慰剂的双盲，交叉研究。结果奥美拉唑组第1天和第3天pH > 4的时间百分比中位数分别为93%（88%-95%）和96%（94%-99%），雷尼替丁组分别为67%（56%-78%）和43%（31%-51%）（均P < 0.001 vs. omeprazole）。第1天和第3天奥美拉唑所需的平均剂量（±SD）分别为235.8 ± 44 mg和134.0 ± 37 mg雷尼替丁剂量分别为502.5 ± 76 mg和541.8 ± 25 mg，结论随着剂量的逐渐降低，奥美拉唑可持续维持胃内pH值在4以上。在72小时内对雷尼替丁输注的抗分泌作用产生了显著的耐受性，尽管个体滴定剂量超过500 mg/24小时，但仍未克服。因此，将单日H2受体阻滞剂和质子泵抑制剂研究的药效学结果应用于应激性溃疡相关出血的长期输注试验是不合适的。
Background/AimsProlonged infusions of H2-antagonists are commonly used in intensive care units, although little is known about their antisecretory efficacy beyond the initial 24 hours of dosing. The aim of this study was to assess the antisecretory effects of infusions of ranitidine and omeprazole for a period of 72 hours.MethodsTwelve healthy volunteers received individually titrated 72-hour intravenous infusions of omeprazole, ranitidine, or placebo in a double-blind, cross-over study. Gastric pH and dosing requirements were compared.ResultsThe median percentage of time with pH > 4 (interquartile range) was 93% (88%–95%) on day 1 and 96% (94%–99%) on day 3 with omeprazole and 67% (56%–78%) and 43% (31%–51%), respectively, with ranitidine (bothP< 0.001 vs. omeprazole). The mean doses (±SD) required on days 1 and 3 for omeprazole were 235.8 ± 44 mg and 134.0 ± 37 mg (P< 0.0001), and ranitidine doses were 502.5 ± 76 mg and 541.8 ± 25 mg, respectively (P= 0.05).ConclusionsOmeprazole infusions consistently maintained gastric pH above 4 over a period of 72 hours with progressively lower doses. Significant tolerance to the antisecretory effect of ranitidine infusion developed in 72 hours, which was not overcome despite individually titrated doses of more than 500 mg/24 hours. Consequently, application of pharmacodynamic results of single-day H2-blocker and proton-pump inhibitor studies to prolonged infusion trials for stress ulcer-related bleeding is inappropriate.