Shimada N, Omuro H, Saka S, Ebihara I, Koide H
Department of Medicine, Koto Hospital, Tokyo, Japan.
Nihon Jinzo Gakkai Shi. 1999 Jun;41(4):460-3.
Theophylline toxicity has been recognized since its introduction into clinical medicine. Clarithromycin is a new oral macrolide antibiotic with excellent antibacterial activity and rare adverse effect. Patients with upper respiratory infection are often treated with theophylline and clarithromycin concurrently. We report a case of acute renal failure due to acute rhabdomyolysis caused by the interaction of theophylline and clarithromycin. A 72-year-old man visited our hospital because of coughing and a sore throat continuing for 1 week. He was diagnosed as having the common cold with a bronchial asthmatic symptom and was prescribed 200 mg/day of sustained-release theophylline for the treatment of asthma for 7 days. One week later, he visited our hospital again. Radiographic study of the chest revealed mild interstitial pneumonia and 200 mg/day of sustained-release theophylline and 400 mg/day of clarithromycin were administrated concomitantly. Five days after the second visit, the patient was admitted to our hospital because of generalized twitching, muscular weakness, high fever and serious general condition. He experienced generalized muscular twitching and tremor. Blood urea nitrogen was 106.1 mg/dl, serum creatinine was 7.4 mg/dl, serum creatinine kinase (CK) was 36,000 IU/l (normal 15-130 IU/l), CK isozyme revealed the following ratio: BB 0%, MB 1% and MM 99%. He was diagnosed as having acute renal failure with rhabdomyolysis caused by the interaction of theophylline and clarithromycin. Hemodialysis therapy was started. After 5 weeks, his serum creatinine was markedly decreased. It is well-known that clarithromycin enhances the serum concentration of theophylline by inhibition of the cytochrome P450-dependent pathway in hepatocytes. Theophylline toxicity may be enhanced when clarithromycin is administrated concomitantly, especially to elderly patients with dehydration.
自引入临床医学以来,人们就认识到了茶碱中毒的问题。克拉霉素是一种新型口服大环内酯类抗生素,具有出色的抗菌活性且不良反应罕见。上呼吸道感染患者常同时接受茶碱和克拉霉素治疗。我们报告一例因茶碱与克拉霉素相互作用导致急性横纹肌溶解进而引发急性肾衰竭的病例。一名72岁男性因咳嗽和咽痛持续1周前来我院就诊。他被诊断为普通感冒伴有支气管哮喘症状,并被处方每日200毫克缓释茶碱用于治疗哮喘,疗程7天。1周后,他再次来我院就诊。胸部影像学检查显示轻度间质性肺炎,遂同时给予每日200毫克缓释茶碱和每日400毫克克拉霉素。第二次就诊5天后,患者因全身抽搐、肌肉无力、高热及严重的全身状况而入院。他出现了全身肌肉抽搐和震颤。血尿素氮为106.1毫克/分升,血清肌酐为7.4毫克/分升,血清肌酸激酶(CK)为36,000国际单位/升(正常范围15 - 130国际单位/升),CK同工酶显示以下比例:BB 0%,MB 1%,MM 99%。他被诊断为因茶碱与克拉霉素相互作用导致急性肾衰竭伴横纹肌溶解。开始进行血液透析治疗。5周后,他的血清肌酐显著下降。众所周知,克拉霉素通过抑制肝细胞中细胞色素P450依赖途径来提高茶碱的血清浓度。当同时使用克拉霉素时,尤其是对脱水的老年患者,茶碱毒性可能会增强。