Pounder R E, Williams J G, Russell R C, Milton-Thompson G J, Misiewicz J J
Gut. 1976 Mar;17(3):161-8. doi: 10.1136/gut.17.3.161.
The effect of cimetidine, a new histamine H2-receptor antagonist, on gastric acid secretion stimulated by a homogenised meal was studied in six normal volunteers using an in vivo intragastric titration technique. The subjects were studied twice, no more than 48 h apart, receiving either cimetidine 200 mg or placebo in random order. Cimetidine administered either 32 men before (three subjects) or with the meal (three subjects) significantly inhibited gastric acid secretion in all the subjects throughout the period of study; 96 min after food, total acid secretion decreased by 67 and 57% respectively. When the drug was taken with the meal absorption was slower (mean peak blood level 2-34 mumol/l, 80-128 min after dosing) than when administered on an empty stomach (mean peak blood level 5-08 mumol/l, 48-64 min after dosing). Blood cimetidine concentration correlated significantly (P less than 0-01) with percentage inhibition of acid output and the calculated concentration resulting in 50% inhibition of gastric acid secretion (IC50) was 1-6 mumol/l. Secretion of gastrin in response to food was unaffected by cimetidine. The results suggest that 200 mg cimetidine effectively inhibits food-stimulated acid secretion and that the bioavailability of the drug may be affected by the timing of dosage in relation to meals. No unwanted effect were observed.
采用体内胃内滴定技术,在6名正常志愿者中研究了新型组胺H2受体拮抗剂西咪替丁对匀浆餐刺激胃酸分泌的影响。受试者接受两次研究,间隔不超过48小时,随机顺序服用200毫克西咪替丁或安慰剂。在进食前(3名受试者)或进食时(3名受试者)服用西咪替丁,在整个研究期间均显著抑制了所有受试者的胃酸分泌;进食后96分钟,总酸分泌分别下降了67%和57%。与空腹服用(给药后48 - 64分钟平均血药峰浓度5.08 μmol/L)相比,餐时服用该药吸收较慢(给药后80 - 128分钟平均血药峰浓度2.34 μmol/L)。血中西咪替丁浓度与胃酸分泌抑制百分比显著相关(P < 0.01),导致胃酸分泌50%抑制的计算浓度(IC50)为1.6 μmol/L。西咪替丁不影响食物刺激引起的胃泌素分泌。结果表明,200毫克西咪替丁能有效抑制食物刺激的胃酸分泌,且药物的生物利用度可能受给药时间与进餐关系的影响。未观察到不良反应。