Lewis G P, Jusko W J
Clin Pharmacol Ther. 1975 Oct;18(4):475-84. doi: 10.1002/cpt1975184475.
Ampicillin pharmacokinetics was studied in 9 cirrhotic patients and in 8 healthy subjects to assess liver disease-related differences in distribution, elimination, and bioavailability of ampicillin. Plasma, urine, and ascites fluid samples were analyzed microbiologically. After intravenous doses, the cirrhotic patients have lower initial plasma concentrations of ampicillin because of the larger volume of distribution. Such patients usually have diminished renal function, which, because renal tubular secretion is the main route of excretion of ampicillin, causes prolonged retention of ampicillin. Metabolic-biliary clearance of ampicillin, normally accounting for removal of only 10% of the dose in normal subjects, is three times as great in cirrhotic patients. Peak ascites fluid concentrations of ampicillin ranged from 2 to 7 mcg/ml after 600 mg iv doses, and very slow clearance of ampicillin from the peritoneal cavity results in persistence in this compartment. Though absorption of ampicillin from capsules was often erratic, its bioavailability was similar in normal and cirrhotic subjects. These findings suggest that the usual course of ampicillin therapy of infections should not be altered in cirrhotic patients. On the other hand, reduction in dosage may be called for when there is renal impairment.
对9名肝硬化患者和8名健康受试者的氨苄西林药代动力学进行了研究，以评估肝病患者在氨苄西林分布、消除和生物利用度方面的差异。采用微生物学方法分析血浆、尿液和腹水样本。静脉给药后，由于分布容积较大，肝硬化患者的氨苄西林初始血浆浓度较低。此类患者通常肾功能减退，由于肾小管分泌是氨苄西林的主要排泄途径，导致氨苄西林潴留时间延长。在正常受试者中，氨苄西林经代谢-胆汁清除的量通常仅占给药剂量的10%，而在肝硬化患者中该清除率增加了两倍。静脉注射600mg氨苄西林后，腹水中氨苄西林的峰值浓度范围为2至7μg/ml，且氨苄西林从腹腔清除非常缓慢，导致其在该腔隙中持续存在。虽然氨苄西林从胶囊中的吸收常常不稳定，但其在正常受试者和肝硬化患者中的生物利用度相似。这些研究结果表明，肝硬化患者氨苄西林治疗感染的常规疗程无需改变。另一方面，肾功能损害时可能需要减少剂量。
