基于PK/PD模型优化加替沙星胃肠道给药方案(1)
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[摘要] 目的 通过建立药代动力学/药效学(PK/PD)模型确定加替沙星胃肠道最佳给药方案。方法 募集40名健康志愿者按3种给药方案(分别为：400mg qd、200mg bid、100mg qid)口服加替沙星片，HPLC-UV法测定血药浓度，求出药代动力学参数即加替沙星对敏感菌的抗菌活性MIC90；用DAS软件拟合出不同给药方案时%T>MIC90，确定加替沙星胃肠道最佳给药方案。结果 根据建立的PK/PD模型拟合结果，3种给药方案的%T>MIC90分别为31.6%、42.6%和17.8%。结论 优化的加替沙星胃肠道给药方案为200mg，bid，此时%T>MIC90符合35%～55%的理想比值。
[关键词] 药代动力学/药效学模型；加替沙星；高效液相色谱法；给药方案
[中图分类号] R969 [文献标识码] B[文章编号] 1673-9701(2011)27-59-03
Optimizing Dosage Regimen of Gatifloxacin by Gastrointestinal Tract Based on Pharmacokinetic-pharmacodynamic Model
TAN Xinghua
Department of Pharmacy, Shaoxing City People’s Hospital of Zhejiang Province, Shaoxing 312000, China
[Abstract] Objective To study dosage regimen of gatifloxacin by gastrointestinal tract based on pharmacokinetic-pharmacodynamic model. Methods The study was conducted in 40 healthy vounteers. After receiving a single dose of 400 mg gatifloxacin tablets on the three dosage regimens(400mg one time a day, 200mg two times a day, 100 mg four times a day). Blood drug concentrations were determined by HPLC-UV and the pharmaeokinetic parameters were calculated by DAS program. The pharmacodynamic parameters were minimal inhibitory concentration(MIC90)of sensitive bacteria. The pharmacokinetic and pharmacodynamic parameters were simulated by DAS program for %T>MIC90 value，and reasonable dosage regimen was calculated. Results The PK/PD model established by DAS suggested that the value of %T>MIC90 of three dosage regimens were 31.6%, 42.6% and 17.8%, respectively. Conclusion To achieve the ideal value 35%-55% of T>MIC90 and more effectiveness, gatifloxacin may be taken orally 200 mg two times a day.
[Key words] Pharmacokinetic-pharmacodynamic model; Gatifloxacin; HPLC; Dosage regimen
加替沙星(gatifloxacin，GTFX)抗菌活性强、抗菌谱广，是第四代氟喹诺酮类抗生素，是氟喹诺酮分子中C7位被3-甲基哌嗪取代后的衍生物，它对许多革兰阴性菌包括流感嗜血杆菌、铜绿假单胞菌、克雷伯菌属、志贺菌属、沙门菌属等均具有较好的抗菌活性，而且对部分革兰阳性球菌包括溶血性链球菌、肠球菌属、肺炎链球菌、葡萄球菌属及脆弱拟杆菌、消化链球菌等厌氧菌也有较好的抗菌活性，被广泛应用于治疗各种敏感致病菌引起的感染[1]。%T>MIC90的理想期望值为35%～55%，而加替沙星24h内的血药浓度大于MIC90的时间低于35%，故该药属于时间依赖型抗菌药[2]。故采用何种给药途径能保证%T>MIC90尚未见报道。本实验通过对健康志愿者口服加替沙星片建立药代动力学/药效学(PK/PD)模型 ......
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