Low Chai Luan, Gopalakrishna Kamani, Lye Wai Choong
Department of Pharmacy, National University of Singapore, Singapore.
National University Hospital, Singapore.
J Am Soc Nephrol. 2000 Jun;11(6):1117-1121. doi: 10.1681/ASN.V1161117.
This study determined the pharmacokinetic characteristics of once daily intraperitoneal (IP) cefazolin in continuous ambulatory peritoneal dialysis (CAPD) patients. Each of the 10 volunteer CAPD patients without active peritonitis received a single IP dose of 1 g of cefazolin sodium for a 6-h dwell. All patients underwent a fixed CAPD regimen comprising a first 6-h dwell followed by two 3-h dwells and a final 12-h overnight dwell. Blood and dialysate samples were collected at 0, 0.5, 1, 2, 3, 6 (end of first dwell), and 24 h after the administration of IP cefazolin. Any urine produced was collected over the 24-h study period. A validated HPLC method was used to analyze cefazolin in plasma, dialysate, and urine. The bioavailability was found to be 77.9 +/- 3.1%, volume of distribution 0.20 +/- 0.05 L/kg, and plasma half-life 39.9 +/- 25.4 h. Mean total, renal, and peritoneal clearances were 4.5 +/- 2.3, 1. 4 +/- 1.1, and 3.5 +/- 1.8 ml/min, respectively. Mean plasma and dialysate concentrations at 24 h were 42.8 +/- 14.3 and 31.8 +/- 11. 7 mcg/ml, respectively, well above the minimum inhibitory concentrations (MIC) of susceptible organisms. A once daily IP cefazolin dose of 500 mg/L gave desirable pharmacokinetic attributes for use as a suitable alternative to vancomycin for empiric treatment of CAPD-associated peritonitis.
本研究确定了持续非卧床腹膜透析(CAPD)患者每日一次腹腔内(IP)注射头孢唑林的药代动力学特征。10名无活动性腹膜炎的CAPD志愿者患者,每人接受1g头孢唑林钠的单次IP剂量,留存6小时。所有患者均采用固定的CAPD方案,包括首次6小时留存,随后两次3小时留存,最后一次12小时过夜留存。在腹腔注射头孢唑林后0、0.5、1、2、3、6小时(首次留存结束时)和24小时采集血液和透析液样本。在24小时的研究期间收集产生的任何尿液。采用经过验证的高效液相色谱法分析血浆、透析液和尿液中的头孢唑林。发现生物利用度为77.9±3.1%,分布容积为0.20±0.05L/kg,血浆半衰期为39.9±25.4小时。平均总清除率、肾清除率和腹膜清除率分别为4.5±2.3、1.4±1.1和3.5±1.8ml/min。24小时时的平均血浆和透析液浓度分别为42.8±14.3和31.8±11.7mcg/ml,远高于敏感菌的最低抑菌浓度(MIC)。每日一次500mg/L的腹腔注射头孢唑林剂量具有理想的药代动力学特性,可作为经验性治疗CAPD相关性腹膜炎时替代万古霉素的合适选择。