Roy A K, Cuda M P, Levine R A
Department of Medicine, State University of New York, SUNY-Health Science Center, Syracuse 13210.
Am J Med. 1988 Oct;85(4):525-7. doi: 10.1016/s0002-9343(88)80089-5.
Theophylline is metabolized by the hepatic microsomal oxidase system, as is ranitidine, although the latter has a much lower affinity for the system. The incidence of theophylline toxicity is rare when the two drugs are administered simultaneously. We observed the development of clinical and chemical toxicity in three elderly patients receiving oral theophylline therapy for chronic obstructive pulmonary disease after the administration of ranitidine therapy for peptic ulcer disease.
Three patients with chronic obstructive pulmonary disease who had been receiving theophylline for prolonged periods of time were studied. Two patients presented with complaints of epigastric pain, which was attributed to acid-peptic disease; the other patient presented with hematemesis, which was shown to be due to gastric and duodenal ulcers. Ranitidine was administered for treatment of acid-peptic disease. Theophylline clearance rates were determined before, during, and after ranitidine treatment. When symptoms of theophylline toxicity developed, the dose of theophylline was either stopped or reduced. Subsequently, patients were readministered their usual dose of theophylline.
The effect of simultaneous administration of both drugs resulted in similar reductions in theophylline clearance rates. Serum theophylline levels returned to pretreatment values after cessation of ranitidine treatment. In one patient, rechallenge with ranitidine during steady-state theophylline treatment resulted in recurrence of clinical and chemical theophylline toxicity.
These observations suggest that treatment with ranitidine may cause clinically apparent interactions with theophylline since both drugs are metabolized by the same cytochrome P-450 isozymes.
茶碱由肝微粒体氧化酶系统代谢，雷尼替丁亦是如此，尽管后者对该系统的亲和力低得多。两种药物同时给药时，茶碱中毒的发生率很低。我们观察到3例患有慢性阻塞性肺疾病并接受口服茶碱治疗的老年患者，在接受雷尼替丁治疗消化性溃疡疾病后出现了临床和化学毒性反应。
研究了3例长期接受茶碱治疗的慢性阻塞性肺疾病患者。2例患者主诉上腹部疼痛，归因于酸相关性疾病；另1例患者出现呕血，结果显示是由胃溃疡和十二指肠溃疡所致。给予雷尼替丁治疗酸相关性疾病。在雷尼替丁治疗前、治疗期间和治疗后测定茶碱清除率。当出现茶碱中毒症状时，停用或减少茶碱剂量。随后，再次给予患者常规剂量的茶碱。
两种药物同时给药导致茶碱清除率出现相似程度的降低。雷尼替丁治疗停止后，血清茶碱水平恢复到治疗前值。在1例患者中，在茶碱稳态治疗期间再次给予雷尼替丁导致茶碱临床和化学毒性反应复发。
这些观察结果表明，雷尼替丁治疗可能会与茶碱发生临床上明显的相互作用，因为两种药物均由相同的细胞色素P-450同工酶代谢。
