Nephrology Clinic, National Cancer Center, Goyang, South Korea.
Antimicrob Agents Chemother. 2011 Jun;55(6):2523-7. doi: 10.1128/AAC.01543-10. Epub 2011 Mar 14.
The pharmacokinetics (PK) of ceftazidime after intravenous (i.v.) administration during automated peritoneal dialysis (APD) and their dependence on peritoneal membrane transport are the targets of the present study. Eleven patients receiving a single i.v. dose of ceftazidime (15 mg/kg of body weight) (seven males, median [interquatile] age, 59 [36 to 62]) were recruited. Serum and dialysate samples were collected at the beginning, middle, and end of each of the five dwells during a 24-h period, with dwells 1, 2, and 3 using an automated cycler (designated on-cycler) and dwells 4 and 5 being manual exchanges (designated off-cycler), together with urine collection during the same period. Population PK analysis was employed to estimate the PK parameters. Peritoneal equilibration tests were performed for all patients, and correlations between peritoneal clearance (CL(PD)) for ceftazidime and dialysate-to-plasma ratios for creatinine (D/P(cr)) were obtained using the Spearman's product correlation coefficient (ρ). Ceftazidime renal clearance (CL(renal)) was 0.052 ml/min/kg, and CL(PD) was 0.063 ± 0.050 ml/min/kg. CL(PD) for on- and off-cycler were 0.071 and 0.058 ml/min/kg (P = 0.164), respectively. A significant correlation between CL(PD) and D/P(cr) was observed, with one outlier excluded, suggesting that CL(PD) for ceftazidime during APD is dependent upon the peritoneal small-solute transport rate. A model prediction yielded adequate serum and dialysate concentrations of ceftazidime throughout a 24-h period for sensitive organisms (MIC, 8 μg/ml) by either i.v. (at 15 mg/kg) or intraperitoneal (i.p.; at 20 mg/kg) administration during off-cycler dwells. The present study suggests that the i.v. administration of ceftazidime at 15 mg/kg or i.p. administration of ceftazidime at 20 mg/kg during a long dwell every 24 h can be recommended for treating systemic or intraperitoneal infections of APD patients.
本研究旨在探讨头孢他啶静脉给药后在自动腹膜透析（APD）期间的药代动力学（PK）及其对腹膜膜转运的依赖性。
招募了 11 名接受单次静脉注射头孢他啶（15mg/kg 体重）（7 名男性，中位数[四分位数]年龄 59[36 至 62]）的患者。在 24 小时期间的每个 5 次停留的开始、中间和结束时收集血清和透析液样本，其中停留 1、2 和 3 使用自动循环器（指定为在线循环器），停留 4 和 5 为手动交换（指定为离线循环器），并在此期间收集尿液。采用群体 PK 分析估算 PK 参数。对所有患者进行腹膜平衡试验，并通过 Spearman 乘积相关系数（ρ）获得头孢他啶腹膜清除率（CL(PD)）与肌酐透析液与血浆比值（D/P(cr)）之间的相关性。头孢他啶肾清除率（CL(renal)）为 0.052ml/min/kg，CL(PD)为 0.063±0.050ml/min/kg。在线循环器和离线循环器的 CL(PD)分别为 0.071 和 0.058ml/min/kg（P=0.164）。排除一个离群值后，观察到 CL(PD)与 D/P(cr)之间存在显著相关性，提示 APD 期间头孢他啶的 CL(PD)取决于腹膜小分子转运率。模型预测表明，通过静脉内（15mg/kg）或腹膜内（20mg/kg）给药，在离线循环器停留期间，头孢他啶的静脉内（15mg/kg）或腹膜内（20mg/kg）给药在 24 小时内可获得足够的血清和透析液浓度，用于治疗敏感菌（MIC，8μg/ml）引起的全身或腹膜内感染。
本研究表明，对于 APD 患者，可推荐每 24 小时进行一次长停留，静脉内给予头孢他啶 15mg/kg 或腹膜内给予头孢他啶 20mg/kg，以治疗全身或腹膜内感染。
