Friedrich L V, White R L, Kays M B, Brundage D M, Yarbrough D
College of Pharmacy, Medical University of South Carolina, Charleston 29425-0810.
Antimicrob Agents Chemother. 1991 Jan;35(1):57-61. doi: 10.1128/AAC.35.1.57.
The pharmacokinetics of aztreonam in eight adult patients with severe burn injuries (total body surface area burn, 49% +/- 21% [mean +/- standard deviation]) were studied. The time of initiation of study following burn injury was 7.0 +/- 1.4 days. Four patients at first dose and at steady state were studied. Aztreonam concentrations were measured by high-performance liquid chromatography, and a two-compartment model was used to fit the data. No significant differences in any pharmacokinetic parameters between first dose and steady state were observed. Volume of distribution of the central compartment after first dose (0.14 liters/kg) and volume of distribution at steady state (0.31 liters/kg) were approximately 30% higher than those reported for other patient populations. Total drug clearance and renal drug clearance when normalized to creatinine clearance (CLCR) were similar to those previously reported for other critically ill patients. CLCR was strongly correlated with renal drug clearance (r = 0.94) and total drug clearance (r = 0.95). The extent and degree of burn (percent second or third degree burn) were poorly correlated with all pharmacokinetic parameters with the exception of the volume of distribution at steady state, which was correlated with both total body surface area burn (r = 0.95) and percent second degree burn (r = 0.83). Aztreonam pharmacokinetics are altered as a result of thermal injury; however, CLCR can be used to assess the clearance of aztreonam in burn patients.
对8例严重烧伤成年患者(烧伤总面积为49%±21%[均值±标准差])氨曲南的药代动力学进行了研究。烧伤后开始研究的时间为7.0±1.4天。对4例患者在首剂和稳态时进行了研究。采用高效液相色谱法测定氨曲南浓度,并使用二室模型拟合数据。未观察到首剂和稳态时任何药代动力学参数有显著差异。首剂后中央室分布容积(0.14升/千克)和稳态时分布容积(0.31升/千克)比其他患者群体报道的值约高30%。以肌酐清除率(CLCR)校正后的总药物清除率和肾药物清除率与先前报道的其他重症患者相似。CLCR与肾药物清除率(r = 0.94)和总药物清除率(r = 0.95)密切相关。烧伤的范围和程度(二度或三度烧伤百分比)与所有药代动力学参数相关性较差,但稳态时分布容积除外,其与烧伤总面积(r = 0.95)和二度烧伤百分比(r = 0.83)均相关。热损伤导致氨曲南药代动力学改变;然而,CLCR可用于评估烧伤患者氨曲南的清除率。