Gugler R, Fuchs G, Dieckmann M, Somogyi A A
Clin Pharmacol Ther. 1981 Jun;29(6):744-8. doi: 10.1038/clpt.1981.105.
Cimetidine plasma concentration-response relationships were investigated in six healthy subjects using suppression of gastric acid secretion under continuous pentagastrin stimulation (1.5 micrograms/kg/hr) as a test model. With the Hill equation the sigmoid was preferable to the linear relationship between plasma concentration and effect, and there were significant correlations of 0.78 micrograms/ml (range 0.54 to 1.04 micrograms/ml) for 50% inhibition of gastric acid secretion was determined; mean concentration for 90% inhibition was calculated to be 3.9 micrograms/ml. The model described should allow determination of whether different patient populations (e.g., healthy subjects, patients with ulcers, male and female patients, patients with renal or liver disease) differ from one another in concentration-response relationships to histamine H2-receptor antagonists, so that appropriate drug plasma levels should be achieved for specific degrees of inhibition of gastric acid secretion.
以持续五肽胃泌素刺激（1.5微克/千克/小时）下胃酸分泌的抑制作为测试模型，在6名健康受试者中研究了西咪替丁的血浆浓度-反应关系。采用希尔方程，血浆浓度与效应之间的S形关系比线性关系更合适，且确定胃酸分泌50%抑制时的血浆浓度为0.78微克/毫升（范围为0.54至1.04微克/毫升）有显著相关性；计算出90%抑制时的平均浓度为3.9微克/毫升。所描述的模型应能确定不同患者群体（如健康受试者、溃疡患者、男性和女性患者、肾脏或肝脏疾病患者）在组胺H2受体拮抗剂的浓度-反应关系上是否彼此不同，以便针对胃酸分泌的特定抑制程度达到适当的药物血浆水平。
