Dammann H G, de Looze S M, Bender W, Labs R
Dept. of Medicine, Bethanian Hospital, Hamburg, FRG.
Scand J Gastroenterol Suppl. 1988;146:121-34. doi: 10.3109/00365528809099138.
Pharmacodynamic studies revealed that 150 mg of roxatidine acetate were optimal in suppressing gastric acid secretion, and that a single bedtime dose of 150 mg was more effective than a dose of 75 mg twice daily in terms of inhibiting nocturnal acid secretion. When administered orally as a capsule containing a granule formulation, the drug displayed modified-release properties, which led to a sustained suppression of gastric acid secretion. Clinical trials revealed that roxatidine acetate, 75 mg twice daily and 150 mg at night, was highly effective in healing duodenal and gastric ulcers and in reducing ulcer pain, over 4, 6, and 8 weeks of therapy. A steady reduction in diameter was observed in those ulcers not completely healed during therapy. The single bedtime dose regimen, while producing the same degree of healing as the divided daily dose during controlled clinical trials, may be of greater value in therapeutic use owing to improved patient compliance. In all efficacy criteria (cure, reduction in ulcer size, and pain relief) there was no significant difference between roxatidine acetate in a total daily dose of 150 mg, ranitidine in a total daily dose of 300 mg, and cimetidine in a total daily dose of 800 mg. Prevention of gastric and duodenal ulcer relapse was achieved by roxatidine acetate, 75 mg at night for 6 months, in about 70% of patients, as determined in open, pilot studies--a rate comparable to those reported for cimetidine and ranitidine. Roxatidine acetate shares with ranitidine an improved safety profile when compared with cimetidine. Human pharmacology studies and short-term and long-term clinical trials have all shown that roxatidine acetate is an exceptionally well tolerated compound, without the antiandrogenic activity and interference with hepatic drug metabolism which have characterized cimetidine treatment. A reason for the improved safety profile of roxatidine acetate may be its greater potency than cimetidine (six times less potent) and ranitidine (half as potent), so that lower doses of roxatidine acetate, representing a lower chemical load, are therapeutically effective. The novel structure of roxatidine acetate probably also underlies the improved safety of the compound.
药效学研究表明，150毫克醋酸罗沙替丁在抑制胃酸分泌方面效果最佳，且就抑制夜间胃酸分泌而言，睡前单次服用150毫克比每日两次服用75毫克更有效。当以含有颗粒制剂的胶囊口服给药时，该药物呈现出缓释特性，从而导致胃酸分泌得到持续抑制。临床试验表明，每日两次服用75毫克以及夜间服用150毫克的醋酸罗沙替丁，在4周、6周和8周的治疗期内，对于治愈十二指肠溃疡和胃溃疡以及减轻溃疡疼痛均非常有效。在治疗期间未完全愈合的溃疡中，观察到其直径稳步缩小。在对照临床试验中，睡前单次给药方案虽然产生的愈合程度与每日分次给药相同，但由于患者依从性提高，在治疗应用中可能具有更大价值。在所有疗效标准（治愈、溃疡大小缩小和疼痛缓解）方面，每日总剂量为150毫克的醋酸罗沙替丁、每日总剂量为300毫克的雷尼替丁和每日总剂量为800毫克的西咪替丁之间没有显著差异。在开放性初步研究中确定，约70%的患者通过夜间服用75毫克醋酸罗沙替丁6个月实现了胃和十二指肠溃疡复发的预防——这一比率与西咪替丁和雷尼替丁报道的比率相当。与西咪替丁相比，醋酸罗沙替丁与雷尼替丁一样具有更好的安全性。人体药理学研究以及短期和长期临床试验均表明，醋酸罗沙替丁是一种耐受性极佳的化合物，没有西咪替丁治疗所具有的抗雄激素活性和对肝脏药物代谢的干扰。醋酸罗沙替丁安全性提高的一个原因可能是其效力比西咪替丁（效力低六倍）和雷尼替丁（效力低一半）更强，因此较低剂量的醋酸罗沙替丁（代表较低的化学负荷）在治疗上是有效的。醋酸罗沙替丁的新颖结构可能也是该化合物安全性提高的基础。
