头孢地尼、头孢泊肟酯、头孢克洛对常见社区感染细菌的抗菌活性及药代动力学/药效学特征比较

Comparison of pharmacokinetics/pharmacodynamics of cefdinir,cefpodoxime proxetil and cefaclor against common bacteria of community acquired infections

目的 比较头孢地尼、头孢泊肟酯与头孢克洛三种药物药代动力学 /药效学参数 ,评估推荐给药方案的合理性。方法 用琼脂稀释法测定三种抗生素对 2 38株临床分离社区感染细菌抗菌活性 ,拉丁方设计研究三种药物在 12名健康男性单剂口服后药代动力学参数 ,利用药代动力学方程和最低抑菌浓度 (MIC)值计算抗菌药物对各种细菌的血药浓度维持在MIC以上时间 (T >MIC)。结果 头孢地尼除对青霉素不敏感肺炎链球菌抗菌活性较差外 ,对其他细菌的MIC90 为 0 0 31～ 1mg/L。头孢泊肟抗菌作用与头孢地尼相似 ,但对葡萄球菌抗菌活性较差。头孢克洛对大多数细菌的抗菌作用不如前两个药物 ;药代动力学研究表明 ,口服头孢克洛 2 5 0mg后药物吸收较快 ,血药峰浓度为 4 95mg/L± 2 4 1mg/L ,消除半衰期 0 6 9h± 0 6h ;口服头孢地尼与头孢泊肟酯 10 0mg后 ,血药浓度达峰时间 (Tmax)、血药峰浓度 (Cmax)与消除半衰期 (T1/2 β)分别为 2 5h± 0 4 8h、0 81mg/L± 0 19mg/L、1 73h± 0 3h与 2 38h± 0 4 3h、1 12mg/L± 0 2 8mg/L、1 92h± 0 5 5h。T >MIC时间测定表明头孢地尼每日 3次给药对多数细菌可达到给药间隙的 4 0 %以上 ,头孢泊肟推荐给药方案对葡萄球菌基本缺乏T>MIC时间 ,头孢克洛口服 2 5 0mg对大多?

Objective To compare the pharmacokinetics/pharmacodynamics property of cefdinir, cefpodoxime proxetil and cefaclor against common bacteria of community acquired infections and evaluate the recommended regimens.Methods The antibacterial activities of 3 agents against 238 clinical isolates were determined by standard agar dilution test and the pharmacokinetics of these antibiotics in male healthy volunteers were conducted in Latin-square manner. The time over MIC (T>MIC) of serum antibiotic concentrations were calculated with pharmacokinetic equation and MIC.Results The value of MIC 90 s cefdinir against these bacterial strains except penicillin non-sensitive pneumococci were 0.031-1 mg/L. Cefpodoxime held similar antibacterial activity with cefdinir, but was less potent against staphylococci. Cefaclor had much higher MIC values than other two drugs. After oral administration of 250 mg cefaclor, the drug concentration quickly reached peak concentration of 4.95 mg/L±2.41 mg/L and the eliminative half time was 0.69 h±0.6 h; the Tmax, Cmax and T 1/2 β of cefdinir and cefpodoxime after oral administration of 100 mg were 2.5 h±0.48 h,0.81 mg/L±0.19 mg/L,1.73 h±0.3 h and 2.38 h±0.43 h,1.12 mg/L±0.28 mg/L,1.92 h±0.55 h, respectively. T>MIC of cefdinir in thrice daily administration were longer than 40% of medication interval against most of the tested isolates; no T>MIC period was found in cefpodoxime against staphylococci and the T>MICs of cefaclor after 250 mg oral administration were shorter than expected values against most bacteria. Conclusion With powerful antibacterial activity, the T>MICs of cefdinir after 100 mg oral administration can meet with the clinical requirement in most infections; PK/PD value of cefpodoxime proxetil against staphylococci is lower than expectancy and 250 mg cefaclor 3 times daily is not enough to the treatment of common community acquired infections, the regimens of cefpodoxime proxetil and cefclor should be furtherly optimized.