CAJ | 학술논문

目的：研究司帕沙星的药代动力学/药效学结合模型（ PK/PD），设计司帕沙星的临床最佳给药方案。方法用琼脂平板二倍稀释法测定司帕沙星对479株分离菌的最低抑菌浓度（ MIC）值。在受试者中进行单次口服司帕沙星片0.1，0.2和0.3 g 药代动力学研究，计算3种剂量给药后的 AUC0-24 h/MIC 的值。以AUC0-24 h/MIC≥125为靶值（肺炎链球菌为AUC0-24 h/MIC≥50），用蒙特卡洛模型进行1×104次模拟，每次重复都根据各自的概率分布以不同AUC0-24 h以及MIC值计算，将获得的累计反应分数（ CFR）＞90％作为最佳临床给药方案。结果0.1 g给药方案仅对沙门菌属的药效学CFR达90％以上；0.2 g给药方案对肺炎链球菌、不动杆菌和甲氧西林敏感的金黄色葡萄球菌（ MSSA ）的药效学CFR达90％以上，其它菌种均需口服0.3 g才能达到满意的临床疗效并能有效预防细菌耐药性产生，其中耐甲氧西林金黄色葡萄球菌（ MRSA）引起的感染应加大用药剂量。结论对于沙门菌属引起的感染，仅需口服0.1g；对肺炎链球菌、不动杆菌和MSSA引起的感染，口服0.2 g；其他细菌引起的感染用药0.3 g；而对于MRSA引起的感染应考虑，加大用药剂量，如0.4 g qd可能会获得满意的临床疗效。
목적：연구사파사성적약대동역학/약효학결합모형（ PK/PD），설계사파사성적림상최가급약방안。방법용경지평판이배희석법측정사파사성대479주분리균적최저억균농도（ MIC）치。재수시자중진행단차구복사파사성편0.1，0.2화0.3 g 약대동역학연구，계산3충제량급약후적 AUC0-24 h/MIC 적치。이AUC0-24 h/MIC≥125위파치（폐염련구균위AUC0-24 h/MIC≥50），용몽특잡락모형진행1×104차모의，매차중복도근거각자적개솔분포이불동AUC0-24 h이급MIC치계산，장획득적루계반응분수（ CFR）＞90％작위최가림상급약방안。결과0.1 g급약방안부대사문균속적약효학CFR체90％이상；0.2 g급약방안대폐염련구균、불동간균화갑양서림민감적금황색포도구균（ MSSA ）적약효학CFR체90％이상，기타균충균수구복0.3 g재능체도만의적림상료효병능유효예방세균내약성산생，기중내갑양서림금황색포도구균（ MRSA）인기적감염응가대용약제량。결론대우사문균속인기적감염，부수구복0.1g；대폐염련구균、불동간균화MSSA인기적감염，구복0.2 g；기타세균인기적감염용약0.3 g；이대우MRSA인기적감염응고필，가대용약제량，여0.4 g qd가능회획득만의적림상료효。
Objective To optimize clinical dosage regimen of sparfloxa-cin through series of pharmacokinetic/pharmacodynamic ( PK/PD ) val-ues.Methods The minimum inhibitory concentration ( MIC ) of spar-floxacin to 479 isolated bacteria were measured by two -fold agar dilution method.To perform pharmacokinetic test after those healthy volunteers were given a single oral dose of 0.1 , 0.2 , 0.3 g of Sparfloxacin , respec-tively.Based on PK/PD theory, calculation of AUC0-24 h/MIC values af-ter three dosages were done.Estimated value of AUC 0-24 h/MIC≥125 was expected to be the target value ( for streptococcus pneumoniae AUC0-24 h/MIC≥50).The Monte Carlo simulation was repeated 1 ×104 times, and the cumulative fraction of response ( CFR) value was calculat-ed according to the respective probability distributions and different AUC0-24 h/MIC and MIC values.The dosage achieving a CFR above 90 percent was recognized as the optimal dosage regimen.Results Given dose of 0.1 g, the pharmacodynamics value CFR was above 90%only to salmonella genera.Given dose of 0.2 g, the pharmacodynamics value CFR was above 90%to Nitrate negative bacillus, Streptococcus pneumoni-ae, Acinetobacter and Methicillin -sensitive Staphylococcus aureus (MSSA).For other strains, oral dose of 0.3 g was needed to not only achieve satisfactory clinical curative effect but also effectively prevent the drug resistance.And for infections caused by Methicillin -resistant Staphylococcus aureus (MRSA), enhanced drug dose should be considered to achieve satisfactory clinical efficacy.Conclusion For infection caused by salmonella genera, oral dose of 0.1 g was a appropriate dosage regimen.For infection caused by Nitrate negative bacillus, Strepto-coccus pneumoniae, Acinetobacter and MSSA, oral dose of 0.2 g was a proper dosage regimen.For infection caused by others, oral dosage regimen of 0.3 g could achieve the expected satisfactory clinical efficacy.And for infections caused by MRSA, an increasing dosage , such as 0.4 mg, could achieve satisfactory clinical curative effect.