Levine R A, Schwartzel E H
Gut. 1984 Jul;25(7):718-22. doi: 10.1136/gut.25.7.718.
The effect of acute administration of indomethacin over 24 hours on basal and histamine stimulated gastric acid secretion was evaluated in seven normal male volunteers. Augmented histamine tests (0.015 mg/kg/h) infused with the antihistamine diphenhydramine hydrochloride (25 mg/h) were performed before and after pretreatment with indomethacin or matching placebo capsules. The dose of indomethacin was 75 mg (sustained release capsules) taken 12 and 24 hours before and 50 mg taken one hour before a two hour histamine infusion test. Indomethacin enhanced basal gastric secretion from 3.5 +/- 0.5 to 6.4 +/- 0.6 mmol/h (p less than 0.01) and histamine stimulated secretion from 48 +/- 6 to 62 +/- 5 mmol/2 h (p less than 0.05). Indomethacin significantly inhibited systemic prostaglandin biosynthesis as measured by urinary excretion (87 +/- 12 vs 41 +/- 6 ng PGE/g creatinine/h) and the drug increased platelet aggregation time two, five, and six fold, respectively, induced by ADP, collagen, and adrenaline. The data indicate that therapeutic doses of indomethacin augmented basal and secretagogue stimulated gastric acid secretion in control subjects. The enhancement of gastric acid secretion by indomethacin may be because of reduced levels of endogenous prostaglandins. Diminished prostaglandin biosynthesis may play a role in indomethacin induced gastric mucosal damage observed in patients receiving the drug.
在7名正常男性志愿者中评估了24小时急性给予吲哚美辛对基础胃酸分泌和组胺刺激胃酸分泌的影响。在用吲哚美辛或匹配的安慰剂胶囊预处理前后，进行了增强组胺试验（0.015 mg/kg/h），同时输注抗组胺药盐酸苯海拉明（25 mg/h）。吲哚美辛的剂量为75 mg（缓释胶囊），在两小时组胺输注试验前12小时和24小时服用，以及在试验前1小时服用50 mg。吲哚美辛使基础胃分泌从3.5±0.5 mmol/h增加至6.4±0.6 mmol/h（p<0.01），组胺刺激的分泌从48±6 mmol/2 h增加至62±5 mmol/2 h（p<0.05）。通过尿排泄量测定，吲哚美辛显著抑制全身前列腺素生物合成（87±12对41±6 ng PGE/g肌酐/h），并且该药物使由ADP、胶原和肾上腺素诱导的血小板聚集时间分别增加了2倍、5倍和6倍。数据表明，治疗剂量的吲哚美辛可增加对照组受试者的基础胃酸分泌和促分泌剂刺激的胃酸分泌。吲哚美辛增强胃酸分泌可能是由于内源性前列腺素水平降低。前列腺素生物合成减少可能在接受该药物的患者中观察到的吲哚美辛诱导的胃黏膜损伤中起作用。
