严重烧伤患者应用万古霉素后痂下水肿液的药代动力学变化

Changes in pharmaeokinetie parameters of vaneomyein in the subeschar tissue fluid in patients with severe burns

目的 了解严重烧伤患者伤后早期应用万古霉素后痂下水肿液的药代动力学变化。方法 选择10例严重烧伤患者，入院后1～2h开始静脉滴注万古霉素500mg，60min匀速滴完。于给药后1、2、4、8、24、48、96、144、192、240h各取痂下水肿液0．5ml，用荧光偏振免疫法测定万古霉素浓度，采用3P97实用药代动力学计算程序处理药物浓度数据，拟合药代动力学模型并计算参数。结果 患者痂下水肿液万古霉素浓度一时间数据以二房室模型拟合为最佳，主要药代动力学参数：分布相半衰期（3．7±2．6）h、消除相半衰期（92±12）h、表观分布容积（26±6）L、曲线下面积（1279±256）μg·h·ml^-1,总体清除率（0．40±0．08）L／h。结论 严重烧伤患者伤后早期使用万古霉素后，该药能较长时间潴留在第三间隙，其抗菌浓度可维持24h以上，有利于防止创面侵袭性感染。

Objective To investigate the changes in pharmacokinetic parameters of vancomycin in the subeschar tissue fluid（STF） at early post-burn stage in patients with severe burns. Methods Ten patients with severe burns were enrolled in the study and received intraveneous injection of 500 mg vancomycin at an even rate within 60 rains 1 to 2 hours after admission. A total of 0.5 ml STF was collected each time and the concentration of vancomycin in the STF was determined by fluorescence polarization immunoassay （FPIA） method at 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 post-burn hours（PBH）. Pharmacokinetic parameters of vancomycin were produced by program 3P97 and statistically analyzed by program package SPSS10.0. Results The STF concentration-time curves of vancomycin were best fit in two compartment model. Phar- macokinetic parameters of vancomycin in the STF were： t1/2α = （3.7 ± 2.6）h, tl/213 = （92 ± 12 ）h, Vc = （26±6）L, AUC=（1279±256） μg· h^-1·ml^-1, CLs=（0.40±0.08） L/h. Conclusion When vanco- mycin is used early after severe burns, the drug can be retained in the third space, and the concentration of the drug can be maintained for over 24hrs, and it is beneficial to form an antibiotic barrier around the wound to prevent an invasive bacterial infection to the burn wound.