Drusano G, Standiford H, Ryan P, McNamee W, Tatem B, Schimpff S
Eur J Clin Microbiol. 1986 Feb;5(1):88-92. doi: 10.1007/BF02013475.
A method was devised for predicting the serum bactericidal activity of new drugs. Six healthy volunteers received 2 g moxalactam, cefoperazone and cefotaxime, respectively, as 30-min infusions in a crossover manner at one-week intervals. The pharmacokinetics of each drug was characterized and the bactericidal activity of the serum 1 h after infusion was measured against panels of six strains of Pseudomonas aeruginosa, six strains of Escherichia coli, six strains of Staphylococcus aureus, and four strains of Klebsiella pneumoniae. The minimum bactericidal concentration of each antibiotic was determined for each organism by the standard NCCLS reference method and the method of Stratton and Reller. On the basis of these values and a serum concentration-time curve constructed from individual patient pharmacokinetic parameters, the bactericidal activity of the serum 1 h after infusion was predicted. These predictions showed a 90% agreement with measured values calculated according to the method of Stratton and Reller, whereas an agreement of 74% was obtained with the reference method. This difference was statistically significant (p less than 0.001).
设计了一种预测新药血清杀菌活性的方法。6名健康志愿者分别接受2克氨曲南、头孢哌酮和头孢噻肟，以交叉方式每隔一周进行30分钟输注。对每种药物的药代动力学进行了表征，并测定了输注后1小时血清对6株铜绿假单胞菌、6株大肠杆菌、6株金黄色葡萄球菌和4株肺炎克雷伯菌的杀菌活性。通过标准的NCCLS参考方法以及Stratton和Reller的方法，为每种微生物确定了每种抗生素的最低杀菌浓度。根据这些值以及由个体患者药代动力学参数构建的血清浓度-时间曲线，预测了输注后1小时血清的杀菌活性。这些预测结果与根据Stratton和Reller方法计算的测量值有90%的一致性，而与参考方法的一致性为74%。这种差异具有统计学意义（p小于0.001）。
