Prediction of the Distribution Volumes of Cefazolin and Tobramycin in Obese Children Based on Physiological Pharmacokinetic Concepts
Prediction of the Distribution Volumes of Cefazolin and Tobramycin in Obese Children Based on Physiological Pharmacokinetic Concepts
复制标题
基于生理药代动力学概念预测头孢唑林和妥布霉素在肥胖儿童中的分布体积
作者：
R. Koshida;E. Nakashima;N. Taniguchi;A. Tsuji;L. Benet;F. Ichimura
为了估计肥胖儿童中抗菌药物的适当剂量，尝试根据根据正常体重儿童的结果构建的生理药代动力学概念来预测这些儿童中的分布容积。采用非房室分析对肥胖程度为 30% 至 80% 的肥胖儿童进行静脉滴注妥布霉素和头孢唑啉后的血清浓度-时间数据。妥布霉素的稳态分布容积（Vss）显着小于正常体重儿童（P < 0.05），而头孢唑林的值几乎与正常体重儿童相同。在正常体重儿童中获得的表达头孢唑林和妥布霉素之间 Vss 差异的方程在肥胖儿童中失败，这表明肥胖儿童的细胞外间隙大幅减少，超过了正常体重儿童的个体间差异。使用方程0.261·{理想体重(kg)+0.4·[总体重(kg)-理想体重(kg)]}预测妥布霉素的Vss值(升)。头孢唑林的 Vss 预测值为 0.3·（妥布霉素的预测 Vss）+ 0.052·总体重（kg）。预测的 Vss 值和观测到的 Vss 值之间具有良好的相关性。
So as to estimate the appropriate dose of antibacterial drugs in obese children, prediction of the volume of distribution in these children was attempted based on physiological pharmacokinetic concepts which had been constructed from results in normal-weight children. Serum concentration–time data after intravenous drip infusions of tobramycin and cefazolin were analyzed using noncompartmental analysis of obese children in whom the degree of obesity ranged from 30 to 80%. Volume of distribution at steady state (Vss) per total body weight of tobramycin was significantly less than that for normal-weight children (P < 0.05), whereas the value of cefazolin was almost equal to that for normal-weight children. The equation to express the difference of Vss between cefazolin and tobramycin obtained in normal-weight children failed in obese children, suggesting that there is a large decrease in the extracellular space in obese children exceeding the interindividual variations in normal-weight children. The Vss value (liter) for tobramycin was predicted by using the equation 0.261 · {ideal body weight (kg) + 0.4 · [total body weight (kg) – ideal body weight (kg)]}. The Vss value of cefazolin was predicted to be 0.3 · (predicted Vss of tobramycin) + 0.052 · total body weight (kg). A good correlation between the predicted and the observed Vss values was obtained.