Pharmacokinetics of cefepime in patients with thermal burn injury
Pharmacokinetics of cefepime in patients with thermal burn injury
复制标题
DOI：
10.1128/aac.43.12.2848
复制
发表时间：
1999-12-01
影响因子：
4.9
通讯作者：
Bosso, JA
中科院分区：
文献类型：
--
作者：
Bonapace, CR;White, RL;Bosso, JA
对 12 名患有热烧伤和疑似或记录感染的成年患者进行了单次 2 g 剂量给药后头孢吡肟的药代动力学评估。给药后24小时内采集连续血液和尿液样本用于头孢吡肟浓度测定。通过高效液相色谱法测定血清和尿液中的头孢吡肟浓度，并且血清浓度适合二室药代动力学模型。研究时的平均年龄（标准差 [SD]）、实际体重 (ABW)、烧伤总表面积百分比和烧伤后天数分别为 41 (13) 岁、84 (22) kg、36 (17)% 和 9 (3) 天。测量的肌酸酐清除率(CLCR)、总清除率(CLT)、肾清除率(CLR)、α相半衰期、β相半衰期和稳态分布容积(V-SS)的平均值(SD)分别为135(31)ml/min、8.8(2.4)升/小时、8.1(2.0)升/小时、0.33(0.14)小时、2.8(0.6)小时、和 0.43 (0.10) 升/千克体重。当通过 CLCR 标准化时，烧伤患者的头孢吡肟 CL 和 CL 与之前报道的健康志愿者的值相似。使用逐步多元回归将 CLT 与 CLCR 和烧伤后天数相关联 (r(2) = 0.861)、CLR 与 CLCR 和烧伤后天数相关联 (r(2) = 0.773)、非肾清除率与三度 (% 3 度) 烧伤百分比和白蛋白浓度 (r(2) = 0.550) 以及仅与 % 3 度烧伤相关的 V-SS (r(2) = 0.624)，使用患者药代动力学参数获得的模拟稳态血清浓度在至少 60% 的给药间隔内超过了头孢吡肟的敏感性解释标准（断点），给药方案为每 8 小时 1 g（q8h）、2 g q8h 和 2 g q12h。尽管我们的患者和健康志愿者之间的药代动力学参数存在差异，但这些给药方案似乎对于类似烧伤患者来说可能是足够的。
The pharmacokinetics of cefepime following administration of a single 2-g dose were evaluated for 12 adult patients with thermal burn injury and suspected or documented infection. Serial blood and urine samples for cefepime concentration determination were obtained for 24 h following drug administration. Serum and urine cefepime concentrations were determined by high-performance liquid chromatography and serum concentrations were fit to a two-compartment pharmacokinetic model. Mean (standard deviation [SD]) age, actual body weight (ABW), percent total body surface area burned, and days postburn at the time of study were 41 (13) years, 84 (22) kg, 36 (17)%, and 9 (3) days, respectively. Mean (SD) measured creatinine clearance (CLCR), total clearance (CLT), renal clearance (CLR), alpha phase half-life, beta phase half-life, and volume of distribution at steady state (V-SS) were 135 (31) ml/min, 8.8 (2.4) liters/h, 8.1 (2.0) liters/h, 0.33 (0.14) h, 2.8 (0.6) h, and 0.43 (0.10) liters/kg ABW respectively. Cefepime CL, and CL, in burn patients were similar to previously reported values for healthy volunteers when normalized by CLCR. Stepwise multiple regression was used to associate CLT with CLCR and days postburn (r(2) = 0.861), CLR with CLCR and days postburn (r(2) = 0.773), nonrenal clearance with percent third-degree (% 3 degrees) burn and albumin concentration (r(2) = 0.550), and V-SS only with % 3 degrees burn (r(2) = 0.624), Simulated steady-state serum concentrations obtained by using the patients' pharmacokinetic parameters exceeded the susceptibility interpretive standard (breakpoint) of cefepime for at least 60% of the dosing interval with dosing regimens of 1 g every 8 h (q8h), 2 g q8h, and 2 g q12h, Despite differences in pharmacokinetic parameters between our patients and healthy volunteers, it appears that these dosing regimens may be adequate in similar burn patients.