头孢丙烯临床药代动力学及药效学研究

Study on clinical pharmacokinetics and pharmacodynamics of cefprozil

目的 :研究头孢丙烯药代动力学参数及其与常见致病菌的体外抗菌活性的关系 ,为临床选择合理给药方案提供依据。方法 :用微生物法测定 1 0名健康志愿者中的头孢丙烯血药浓度 ,根据血药浓度 时间曲线求算药代动力学参数 ;以平皿二倍稀释法测定头孢丙烯对常见致病菌的体外抗菌活性。结果 :头孢丙烯 5 0 0mg单次口服给药的体内过程符合二室模型。血药浓度峰值 (cmax)为 (9.36± 1 .1 8)mg/L ,达峰时间 (tmax)为 (1 .2 3± 0 .4 5 )h ,血浆清除半衰期 (t1 /2β)为 (1 .31± 0 .35 )h ,血药浓度 时间曲线下面积 (AUC0 ∞)为 (2 7.0 9± 3.0 6 )h·mg/L ,清除率 (CL)为 (1 8.6 9± 2 .30 )L/h。对社区获得性感染的常见致病菌如肺炎链球菌、酿脓链球菌、流感嗜血杆菌、甲氧西林敏感金黄色葡萄球菌 (MSSA )等的最低抑菌浓度 (MIC)值范围为0 .0 1 6～ 4mg/L ;其中 ,单次口服头孢丙烯 5 0 0mg ,对酿脓链球菌感染可达到T >MIC约 4 0 %以上 ,其他致病菌则小于 30 %。结论 :对确诊为社区获得性呼吸道感染常见的致病菌———酿脓链球菌引起的感染 ,头孢丙烯 5 0 0mg ,每日 1次给药 ,可有较好的疗效 ,但对于肺炎链球菌、流感嗜血杆菌和MSSA等 ,建议增加给药次数或增大单次给药剂量 。

Objective: The pharmacokinetic parameters in 10 healthy volunteers and the in vitro antibacterial activity of cefprozil were evaluated. Methods: 10 healthy volunteers received a single dose of 500 mg cefprozil tablet. The serum concentrations of cefprozil were measured by bioassay. The MIC of cefprozil against common bacteria were measured by agar dilution method. Results: The main pharmacokinetic parameters were as follows: c max (9.36±1.18) mg/L, t max (1.23±0.45) h, t 1/2β (1.31±0.35) h, AUC 0 ∞ (27.09±3.06) h·mg/L and CL (18.69±2.30) L/h. The MICs of cefprozil against S.pyogenes, S.pnumoniae, S.aureus (MSSA), and H.influenzae, were in the range of 0.016-4 mg/L. After a single oral dose of cefprozil 500 mg, the T>MIC against S. pyogenes ,attained more than 40% of the dosing interval (i.e. T>MIC nearly 40%). However, T>MIC against other pathogens were <30%. Conclusions: Cefprozil 500 mg q.d. orally may be effective against upper respiratory infections caused by S. pyogenes, however higher daily dose may be needed for the treatment of respiratory tract infections caused by S. pnenmoniae, H influenzae and MSSA.