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头孢唑肟钠静脉滴注治疗社区获得性肺炎的药代动力学与药效学研究

A Pharmacokinetic and Pharmacodynamic Study on Intravenous Cefazedone Sodium in Patients with Community-acquired Pneumonia.

作者信息

Gao Lei, Zhu Yan, Lyu Yuan, Hao Feng-Lan, Zhang Pu, Wei Min-Ji

机构信息

Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100034, China.

出版信息

Chin Med J (Engl). 2015 May 5;128(9):1160-4. doi: 10.4103/0366-6999.156086.

Abstract

BACKGROUND

As a time-dependent antibiotic, the time of cefazedone concentration exceeds the minimum inhibitory concentration (MIC) is the key pharmacokinetic-pharmacodynamic (PK-PD) variable associated with the killing of pathogens. The purpose of the study was to evaluate the clinical regimen rationality of intravenous cefazedone sodium in the treatment of community-acquired pneumonia (CAP) by PK/PD study.

METHODS

Ten patients with mild to moderate CAP were enrolled to receive intravenous cefazedone sodium (2 g q12 h) for 7-14 days. Blood samples were collected in any day during day 5-7. Sputum specimens were collected before treatment for bacteria isolated, and susceptibility to cefazedone determined. PK-PD analysis was performed using the noncompartmental analysis of Phoenix WinNolin software (version 6.1, Pharsight Corporation, CA, USA). The maximal time above MIC (ƒT > MIC) was calculated, and its correlation with clinical efficacy was analyzed.

RESULTS

All 10 patients completed the study and 8 of them were cured. Six strains were isolated from patients before treatment (one for each patient) and all susceptible to cefazedone. Five patients of six in culture positive group were cured. All pathogens were cleared at the end of therapy. The MICs were between 0.25 and 1 mg/L. The main PK parameters were C max 175.22 ± 36.28 mg/L; T½ 1.52 ± 0.23 h; AUC (0-∞) 280.51 ± 68.17 mg·L -1·h -1 ; CL 7.37 ± 1.84 L/h; Vd 16.06 ± 4.42 L. The average ƒT > MIC was 55.45 ± 8.12%.

CONCLUSIONS

Intravenous injection of cefazodone sodium with 2 g q12 h dosage regimen is used in the treatment of CAP caused by sensitive bacteria, either ƒT > MIC or clinical efficacy shows that such dosing regimen is reasonable.

摘要

背景

作为一种时间依赖性抗生素,头孢唑林浓度超过最低抑菌浓度(MIC)的时间是与病原体杀灭相关的关键药代动力学-药效学(PK-PD)变量。本研究的目的是通过PK/PD研究评估静脉注射头孢唑林钠治疗社区获得性肺炎(CAP)的临床用药方案合理性。

方法

纳入10例轻至中度CAP患者,接受静脉注射头孢唑林钠(2g,每12小时1次)治疗7-14天。在第5-7天的任意一天采集血样。治疗前采集痰标本进行细菌分离,并测定对头孢唑林的敏感性。使用Phoenix WinNolin软件(版本6.1,美国加利福尼亚州Pharsight公司)的非房室分析进行PK-PD分析。计算高于MIC的最大时间(ƒT > MIC),并分析其与临床疗效的相关性。

结果

10例患者均完成研究,其中8例治愈。治疗前从患者中分离出6株菌株(每位患者1株),均对头孢唑林敏感。培养阳性组的6例患者中有5例治愈。治疗结束时所有病原体均被清除。MIC在0.25至1mg/L之间。主要PK参数为:Cmax 175.22±36.28mg/L;T½ 1.52±0.23小时;AUC(0-∞)280.51±68.17mg·L-1·h-1;CL 7.37±1.84L/h;Vd 16.06±4.42L。平均ƒT > MIC为55.45±8.12%。

结论

静脉注射头孢唑林钠,2g每12小时1次的给药方案用于治疗由敏感菌引起的CAP,无论是ƒT > MIC还是临床疗效均表明该给药方案合理。

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