毒理性
由于其使用受限，利福喷丁对肝脏的影响不如利福平明确，但它们可能是相似的。因此，长期使用利福喷丁治疗与2%至7%的患者血清转氨酶水平轻微、短暂升高有关，这些异常通常不需要调整剂量或停药。临床上明显的利福喷丁引起的肝损伤尚未有报道，但它可能像利福平一样有可能导致急性肝损伤。由于利福喷丁通常与异烟肼和/或吡嗪酰胺联合使用，后两者也是已知的肝毒性药物，因此在利福喷丁含有方案的急性肝损伤患者中，很难将病因归咎于单一药物，一些证据表明这些联合用药比单一药物更有可能引起损伤。通常，利福霉素引起的损伤发生在1到6周内，血清酶模式在损伤初期通常是肝细胞型，但可能与胆汁淤积和混合型相比。由于利福霉素肝毒性导致的肝外表现，如发热、皮疹、关节痛、水肿和嗜酸性粒细胞增多是不常见的，自体抗体形成也是如此。这种肝毒性的潜力尚未特别证明利福喷丁具有。
Because of its limited use, the effects of rifapentine on the liver have been less well defined than those of rifampin, but they are likely to be similar. Thus, long term therapy with rifapentine is associated with minor, transient elevations in serum aminotransferase levels in 2% to 7% of patients, abnormalities that usually do not require dose adjustment or discontinuation. Clinically apparent liver injury due to rifapentine has not been reported, but it is likely to be similar to rifampin in its potential for causing acute liver injury. Because rifapentine is usually given in combination with isoniazid and/or pyrazinamide, two other known hepatotoxic agents, the cause of the acute liver injury in patients on rifapentine containing regimens may be difficult to relate to a single agent, and some evidence suggests that these combinations are more likely to cause injury than the individual drugs. Typically, the onset of injury due to rifamycins is within 1 to 6 weeks and the serum enzyme pattern is usually hepatocellular at the onset of injury, but can cholestatic and mixed in contrast to isoniazid and pyrazinamide. Extrahepatic manifestations due to rifamycin hepatotoxicity such as fever, rash, arthralgias, edema and eosinophilia are uncommon as is autoantibody formation. This potential for hepatotoxicity has not been specifically demonstrated for rifapentine.
来源:LiverTox
