临床药师掌握P450知识的重要性

从注册论坛会员到今天4天，看了论坛的大量资料，发现从P450角度对临床用药合理性评价方面的资料所占比较低，结合本人工作中发现的问题，感觉临床药师掌握P450知识可以发现预防并阻止临床用药可能存在的风险。
    茶碱控释片哮喘患者常用并需长期使用的药物，克拉霉素呼吸道感染常用及临床也较为频繁使用的抗菌素，患者使用茶碱控释片期间，偶使用克拉霉素的情况临床也多见。从常规合理用药方法分析，较难发现两药合用潜藏的安全性风险。克拉霉素是P450s抑制剂，患者因使用克拉霉素，改变体内茶碱的代谢而致横纹肌溶解。
    在论坛资料中论述均从药物角度考察合理用药，从患者身体状况，饮食等方面探讨的资料自己还未见到，实际上，患者饮食，身体状况对自身P450同工酶活性的影响较大，如： 身体肥胖及患有糖尿病者或饮酒，可使CYP2E1活性增高，而CYP2E1 是对乙酰氨基酚体内生物转化酶，其经CYP2E1催化氧化代谢生成中间产物N-乙酰-对-苯醌亚胺（NOPQI）可引起肝细胞坏死产生肝毒性，CYP2E1活性增高可使对乙酰氨基酚的肝毒性增加。
    临床药师的职责是使药物使用的合理性提高，因此，尽可能地掌握更多的知识，才能提高自己的职业技能。

请告知资料出处好吗？

“患者因使用克拉霉素，改变体内茶碱的代谢而致横纹肌溶解”此句尤其令人费解，茶碱和克拉霉素均无导致横纹肌溶解的作用啊？

A case of acute renal failure with rhabdomyolysis caused by the interaction of theophylline and clarithromycin
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.

谢谢！

上面文献出自1999年“Japanese Journal of Nephrology”杂志的个案报道。经查茶碱确有引起横纹肌溶解的可能，多与患者高龄、茶碱超剂量用药以及药物相互作用有关.......

谢谢LZ的提示。这样学知识印象真是深刻....

非常有意义的知识拾零。
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一例茶碱和克拉霉素的相互作用引起横纹肌溶解症而导致急性肾功能衰竭病例，自从茶碱引入到临床医学它的毒性已被认知。克拉霉素是一种新的具有优良的抗菌活性和不良反应少口服大环内酯类抗生素。上呼吸道感染的病人往往同时使用茶碱和克拉霉素。我们报道一例由于茶碱和克拉霉素相互作用引起的急性横纹肌溶解症而导致急性肾功能衰竭的病例。一名72岁男子因为咳嗽喉咙痛持续1周来我院就诊。他被诊断为伴支气管哮喘的症状的普通感冒，开具200毫克/天缓释茶碱治疗哮喘7天量。一个星期后，他再次来我院。胸部X线的显示，轻度间质性肺炎，给予缓释茶碱200毫克/天加克拉霉素400毫克/天。 5天后的第二次随访，病人因全身抽搐，肌肉无力，高烧被送入我院。他检查全身肌肉痉挛和震颤。尿素氮为106.1毫克/分升，血肌酐为7.4毫克/分升，血清肌酐激酶（CK）是36,000国际单位/升（正常15-130国际单位/升），肌酸激酶同工酶显示BB 0％，MB1％和MM 99％。他被诊断为茶碱和克拉霉素的相互作用引起的急性横纹肌溶解而导致肾功能衰竭。进行血液透析治疗。 5周后，他的血肌酐明显降低。这是众所周知，克拉霉素通过抑制细胞色素P450增强了依赖在肝细胞细胞色素P450途径代谢的茶碱血药浓度。当克拉霉素与茶碱同时使用时茶碱的毒性可能提高，尤其是对脱水老年病人。简单翻译一下望指正。