Inafuku M, Suzuki T, Ohtsu F, Hariya Y, Nagasawa K, Yoshioka Y, Nakahara Y, Hayakawa H
Department of Internal Medicine, Nippon Medical School, Tama Nagayama Hospital, Tokyo.
J Cardiol. 1992;22(1):227-33.
Reported side effects of mexiletine, a useful drug for managing premature ventricular contractions (PVC) and ventricular tachycardia (VT), are gastrointestinal symptoms including nausea and vomiting. Theophylline, a bronchodilator, also causes similar gastrointestinal symptoms with its frequency proportional to the increases in its serum concentration. The occurrence of gastrointestinal symptoms is known to increase in combination therapy of mexiletine and theophylline. However, the pharmacokinetic interaction between mexiletine and theophylline has not been clarified. We, therefore, investigated the effects of mexiletine on theophylline pharmacokinetics. Three patients with bronchial asthma complicating PVC and/or VT (one male and 2 females, aged 70.0 +/- 13.1 years) were studied. All patients were given prophylactic theophylline anticipatory for asthmatic attacks, which was followed by oral administration of mexiletine, 200-300 mg daily, for PVC and/or VT. The serum theophylline concentrations in 3 cases were increased from 13.8 to 25.3 micrograms/ml, from 14.6 to 27.8 micrograms/ml, and from 10.4 to 15.4 micrograms/ml, respectively, after the administration of mexiletine. However, significant decreases in theophylline clearance were observed after the administration of mexiletine by 46, 47 and 35%, respectively. (p < 0.05) With a decrease in theophylline dosage, the serum theophylline concentrations decreased, and gastrointestinal symptoms resolved. Theophylline is metabolized mainly in the liver through an oxidative reaction of p-450 enzyme, however, its metabolism is affected by many factors, such as medications and complications. The results of this study indicated that mexiletine decreases the theophylline clearance by inhibiting the p-450 oxidative reaction to theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)
美西律是一种用于治疗室性早搏（PVC）和室性心动过速（VT）的有效药物，其报告的副作用是胃肠道症状，包括恶心和呕吐。支气管扩张剂茶碱也会引起类似的胃肠道症状，其发生频率与血清浓度的升高成正比。已知在美西律和茶碱的联合治疗中，胃肠道症状的发生率会增加。然而，美西律和茶碱之间的药代动力学相互作用尚未阐明。因此，我们研究了美西律对茶碱药代动力学的影响。研究了3例合并PVC和/或VT的支气管哮喘患者（1例男性和2例女性，年龄70.0±13.1岁）。所有患者均预防性服用茶碱以预防哮喘发作，随后口服美西律，每日200 - 300mg，用于治疗PVC和/或VT。服用美西律后，3例患者的血清茶碱浓度分别从13.8微克/毫升升至25.3微克/毫升、从14.6微克/毫升升至27.8微克/毫升、从10.4微克/毫升升至15.4微克/毫升。然而，服用美西律后，茶碱清除率分别显著下降了46%、47%和35%。（p < 0.05）随着茶碱剂量的减少，血清茶碱浓度降低，胃肠道症状缓解。茶碱主要在肝脏中通过p - 450酶的氧化反应进行代谢，然而，其代谢受许多因素影响，如药物和并发症。本研究结果表明，美西律通过抑制对茶碱的p - 450氧化反应降低了茶碱清除率。（摘要截选至250字）
