毒理性
血清氨基转移酶水平升高发生在2%至6%接受达托霉素治疗的患者中，这个比率与安慰剂或比较药物相比略有增加。升高通常是轻到中度的、无症状的，并且是自限性的，经常在不中断治疗甚至不停止治疗的情况下就能解决。有报告称，个别病例可能因达托霉素导致肝损伤，但在大多数情况下血清胆红素正常，血清氨基转移酶升高是轻到中度的，通常伴有严重的肌肉损伤和明显的肌酸激酶升高。没有黄疸或碱性磷酸酶升高的此类病例更可能是由于肌肉而非肝脏损伤。尽管如此，已有报告称，在没有黄疸或碱性磷酸酶升高的情况下，出现了轻度黄疸、血清酶升高呈肝细胞模式和肌酸激酶水平正常的少数病例。发病的潜伏期为5周，没有出现免疫过敏和自身免疫特征，解决过程缓慢，6周后仍存在轻度异常。因此，临床上明显的达托霉素引起的肝损伤可能发生，但非常罕见。
Elevations in serum aminotransferase levels occur in 2% to 6% of patients receiving daptomycin, rates that are minimally higher than with placebo or comparator drugs. The elevations are generally mild-to-moderate, asymptomatic and self-limited, frequently resolving without discontinuation or even interruption of therapy. Isolated case reports of possible liver injury from daptomycin have been reported, but serum bilirubin was normal in most cases, and the serum aminotransferase elevations were mild-to-moderate and typically accompanied by severe muscle injury with marked CK elevations. Such cases without jaundice or alkaline phosphatase elevations are more likely due to muscle rather than liver injury. Nevertheless, a few case reports of mild jaundice with a hepatocellular pattern of serum enzyme elevations and normal CK levels has been published. The latency to onset was 5 weeks, immunoallergic and autoimmune features were not present, and resolution was slow with mild abnormalities still present 6 weeks later. Thus, clinically apparent liver injury from daptomycin probably occurs, but is quite rare.
来源:LiverTox
