基于PK/PD模型的头孢克洛给药方案

Dosage regimen of cefaclor based on pharmacokinetic-pharmacodynamic model

目的根据建立的头孢克洛(第2代头孢类抗生素)药代动力学/药效学(PK/PD)模型建立经胃肠道的给药方案。方法10健康志愿者按3种给药方案(500mg每日3、4、5次)口服头孢克洛,HPLC法测定血药浓度,求出药代动力学参数即头孢克洛对敏感菌的抗菌活性MIC90;用CAPP软件,拟合出不同给药方案时T>MIC90的百分值,推算出较为合理的给药方案。结果建立的PK/PD模型CAPP软件拟合结果,3种给药方案的T>MIC90时间的百分值分别为25.5%、34.0%和42.5%。结论如果头孢克洛预达T>MIC9035%～55%的理想比值,较合理的口服给药方案为500mg每日4次。

Objective To study dosage regimen of cefaclor based on pharmacokinetic-pharmacodynamic model by gastrointestinal route. Methods The study was conducted in ten healthy vounteers. After receiving a single dose of 500 mg cefaclor dispersible tablets on the three dosage regimen （500 mg three times a day ;500 mg four times a day ;500 mg five times a day）. Blood drug concentration were determined by HPLC-UV and the pharmacokinetic parameters were calculated by CAPP program. The pharmacodynamic parameters were minimal inhibitory concentration （MIC90） of sensitive bacteria. The pharmacokinetic and pharmacodynamic parameters were simulated by CAPP program for T 〉 MIC90 value, and reasonable dosage regimen was calculated. Results The PK/PD model established by CAPP suggest that the value of T 〉 MIC90 of three dosage regimen was 25.5% , 34. 0% and 42. 5% , respectively. Conclusion To achieve the ideal value 35%-55% of T 〉 MICgo and more effectiveness, cefaclor may be taken orally 500 mg four times a day.