ABSTRACT
<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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%.</p><p><b>CONCLUSIONS</b>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.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Administration, Intravenous , Anti-Bacterial Agents , Pharmacokinetics , Therapeutic Uses , Cefazolin , Pharmacokinetics , Therapeutic Uses , Community-Acquired Infections , Drug Therapy , Metabolism , Microbial Sensitivity TestsABSTRACT
Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is a widely used technique in the quantitative analysis of small molecules, part of peptides and proteins in biological matrix. When compared with LC, the LC-MS/MS posesses many advantages, such as high sample throughput, high sensitivity and resolutions, simple method development and simultaneous quantification of multiple components. At the stage of method development, the main practices for analysts are to validate analytical methods according to the regulated requirements. However, due to the quantitative mechanisms of LC-MS/MS, even though the used method is fully validated, analytical inaccuracy problem, which is the so called bioanalytical risk (pitfalls), may still exist, if we do not pay attentions to some details. In the present paper, the factors which may cause inaccuracy in quantitative analysis are summarized, especially those could not be found during routine method validation. Those factors include back transformation of unstable drug metabolites to analyte in the handling of biosamples, matrix effects, in-source conversion, and ion interference caused by ions with similar or same mass-to-charge ratio, etc. In addition to QA/QC oversight and strict method validation, the preventing strategies may contain the follows: selecting biosample processing method with high proficiency in eliminating matrix interferences, enhancing chromatographic separation, selection of suitable precursor-product ions and validation with incurred samples, etc.