Deziel-Evans L M, Murphy J E, Job M L
Clin Pharm. 1986 Apr;5(4):319-24.
The influence of five pharmacokinetic indices on therapeutic response was retrospectively studied in 45 adult patients treated with aminoglycosides for bacterial infections. Subjects were treated for a minimum of five days, had culture and sensitivity reports, and had at least one set of steady-state peak and trough serum aminoglycoside concentrations. Serum drug concentrations were determined by enzyme-multiplied immunoassay or by fluorescence polarization assay. Minimum inhibitory concentrations (MICs) for the drugs were determined by microdilution assays. Cure was determined by negative cultures or absence of clinical evidence of infection. Values for five pharmacokinetic indices were determined for each patient: ratio of steady-state peak serum concentration to MIC (Cssmax/MIC); time that the serum concentration remained above the MIC during a 72-hour period (tsupra-MIC(72)); the intensity index for a 72-hour period (II(72)), which is related but not identical to the area under the curve (AUC), reflecting the contributions of Cssmax/MIC and tsupra-MIC(72); time that the serum concentration was greater than four times the MIC during a 72-hour period (tsupra-(4 X MIC)(72)), and the intensity index related but not identical to AUC greater than four times the MIC (II4 X MIC(72)), which reflects the contribution of Cssmax/(4 X MIC) and tsupra-(4 X MIC)(72). Statistical analysis revealed significant correlations between each of the five indices and the patients' therapeutic responses. The following index values were associated with cures: Cssmax/MIC greater than 4 (and ideally greater than 8); tsupra-MIC(72) of at least 40 hours; tsupra-(4 X MIC)(72) of at least 10 hours; (4) II(72) greater than 400; and II4 X MIC(72) greater than 50. All five pharmacokinetic indices were good predictors of patient outcome. The ratio of maximum steady-state serum aminoglycoside concentration to minimum inhibitory concentration is the index most easily monitored and interpreted.
回顾性研究了5个药代动力学指标对45例接受氨基糖苷类药物治疗细菌感染的成年患者治疗反应的影响。受试者接受治疗至少5天，有培养和药敏报告，且至少有一组稳态峰浓度和谷浓度血清氨基糖苷类药物浓度。血清药物浓度通过酶放大免疫测定法或荧光偏振测定法测定。药物的最低抑菌浓度（MIC）通过微量稀释法测定。治愈通过培养阴性或无感染的临床证据来确定。为每位患者测定5个药代动力学指标的值：稳态峰血清浓度与MIC之比（Cssmax/MIC）；血清浓度在72小时内保持高于MIC的时间（tsupra-MIC(72)）；72小时的强度指数（II(72)），它与曲线下面积（AUC）相关但不相同，反映了Cssmax/MIC和tsupra-MIC(72)的作用；血清浓度在72小时内大于4倍MIC的时间（tsupra-(4 X MIC)(72)），以及与大于4倍MIC的AUC相关但不相同的强度指数（II4 X MIC(72)），它反映了Cssmax/(4 X MIC)和tsupra-(4 X MIC)(72)的作用。统计分析显示这5个指标中的每一个与患者的治疗反应之间均存在显著相关性。以下指标值与治愈相关：Cssmax/MIC大于4（理想情况下大于8）；tsupra-MIC(72)至少40小时；tsupra-(4 X MIC)(72)至少10小时；II(72)大于400；以及II4 X MIC(72)大于50。所有5个药代动力学指标都是患者预后的良好预测指标。最大稳态血清氨基糖苷类药物浓度与最低抑菌浓度之比是最易于监测和解释的指标。
