Blum R A, Kohli R K, Harrison N J, Schentag J J
Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York 14209.
Antimicrob Agents Chemother. 1989 Sep;33(9):1470-6. doi: 10.1128/AAC.33.9.1470.
The single-dose pharmacokinetics of intravenously administered ampicillin (2.0 g) and sulbactam (1.0 g) were studied in normal subjects and in patients with various degrees of creatinine clearance (CLCR). Six normal subjects (CLCR, greater than 60 ml/min), six patients with mild renal failure (CLCR, 31 to 60 ml/min), four patients with severe renal failure (CLCR, 7 to 30 ml/min), and four patients requiring maintenance hemodialysis (CLCR, less than 7 ml/min) were studied. The terminal half-lives for ampicillin and sulbactam more than doubled in patients with severe renal failure compared with subjects with normal renal function and mild renal insufficiency. CLCR significantly correlated with ampicillin (r = 0.88) and sulbactam (r = 0.54) total body clearance. Mean steady-state volume of distribution and nonrenal clearance for ampicillin and sulbactam were not affected by renal function. Hemodialysis approximately doubled the ampicillin and sulbactam total body clearance. Mean totals of 34.8 +/- 4.0% of the ampicillin dose and 44.7 +/- 3.2% of the sulbactam dose were removed during a 4-h hemodialysis treatment. A slight rebound in concentrations in serum after hemodialysis was observed for both drugs in all four subjects. In hemodialysis patients, the ampicillin half-life was 17.4 +/- 8.0 h and the sulbactam half-life was 13.4 +/- 7.4 h. The ampicillin and sulbactam half-lives were appreciably altered during the hemodialysis period (means of 2.2 and 2.3 h, respectively). The nearly parallel decrease in total body clearance, with volume of distribution and nonrenal clearance remaining relatively constant, suggests that the same ratio of ampicillin to sulbactam is appropriate regardless of renal function. An adjustment of the ampicillin (2.0 g) and sulbactam (1.0 g) dose to twice daily would be appropriate in patients with a CLCR between 7 and 30 ml/min. Doses should be given every 24 h for those undergoing maintenance hemodialysis. On hemodialysis days, doses should be given after hemodialysis.
在正常受试者以及不同程度肌酐清除率（CLCR）的患者中研究了静脉注射氨苄西林（2.0 g）和舒巴坦（1.0 g）的单剂量药代动力学。研究对象包括6名正常受试者（CLCR大于60 ml/分钟）、6名轻度肾衰竭患者（CLCR为31至60 ml/分钟）、4名重度肾衰竭患者（CLCR为7至30 ml/分钟）以及4名需要维持性血液透析的患者（CLCR小于7 ml/分钟）。与肾功能正常和轻度肾功能不全的受试者相比，重度肾衰竭患者中氨苄西林和舒巴坦的终末半衰期延长了一倍多。CLCR与氨苄西林（r = 0.88）和舒巴坦（r = 0.54）的总体清除率显著相关。氨苄西林和舒巴坦的平均稳态分布容积和非肾清除率不受肾功能影响。血液透析使氨苄西林和舒巴坦的总体清除率增加了约一倍。在4小时的血液透析治疗期间，平均清除了34.8±4.0%的氨苄西林剂量和44.7±3.2%的舒巴坦剂量。在所有4名受试者中，两种药物在血液透析后血清浓度均出现轻微反弹。在血液透析患者中，氨苄西林半衰期为17.4±8.0小时，舒巴坦半衰期为13.4±7.4小时。在血液透析期间，氨苄西林和舒巴坦的半衰期明显改变（分别为2.2小时和2.3小时）。总体清除率几乎平行下降，分布容积和非肾清除率相对保持恒定，这表明无论肾功能如何，氨苄西林与舒巴坦的相同比例都是合适的。对于CLCR在7至30 ml/分钟的患者，将氨苄西林（2.0 g）和舒巴坦（1.0 g）剂量调整为每日两次是合适的。对于接受维持性血液透析的患者，应每24小时给药一次。在血液透析日，应在血液透析后给药。
