Anti-PcrV titers in non-cystic fibrosis patients with Pseudomonas aeruginosa respiratory tract infection.

OBJECTIVE: The epidemiology and role of the anti-PcrV titer in non-cystic fibrosis patients with Pseudomonas aeruginosa airway tract infections is not fully understood. This study was performed to compare the anti-PcrV titers of patients with and without P. aeruginosa respiratory tract infections. METHODS: This prospective cohort study was conducted at Hokkaido University Hospital in Japan. Participants had blood and sputum specimens collected on admission. They were divided into two groups based on their sputum culture results. Those with a P. aeruginosa infection were assigned to the P. aeruginosa (PA) group and those without a P. aeruginosa infection were assigned to the non-PA group. Serum anti-PcrV titers were measured using a validated ELISA. RESULTS: Of the 44 participants, 15 were assigned to the PA group and 29 were assigned to the non-PA group. In the PA group, 10/15 participants (66.7%) had an anti-PcrV titer >1000ng/ml compared to 3/29 participants (10.3%) in the non-PA group (p<0.001). In the PA group, two of the five participants with an anti-PcrV titer <1000 ng/ml died of recurrent P. aeruginosa pneumonia; the other three participants did not develop pneumonia. CONCLUSION: The anti-PcrV titers in participants with P. aeruginosa infection varied considerably. Patients with low anti-PcrV titers and refractory P. aeruginosa infections need to be monitored closely.

Development of a novel high-throughput analytical methodology, multiple injection method, for quantitative analysis in drug metabolism and pharmacokinetic studies using liquid chromatography with tandem mass spectrometry.

In this study, we developed a novel methodology, multiple injection method (MIM), for higher-throughput screening of compounds by liquid chromatography-tandem mass spectrometry (LC-MS/MS). MIM involves continuous injections of multiple samples containing a different compound respectively into the column, and then temporarily trapping of analytes at the column head in high-pressure liquid chromatography (HPLC) system. This is followed by elution of all the compounds from the column and detection of them by MS/MS. In this study, fexofenadine, verapamil, risperidone, ondansetron, and imipramine were used as model compounds to investigate the effectiveness of MIM in pharmacokinetic studies. Analytical time of validation samples of these model compounds could be shortened to one third by MIM, compared with the conventional method. In addition, both the accuracy and precision of MIM met the general criteria for quantitative analysis. The peak intensity was found to be unaffected by overlapping compounds even if they have wide range of ionization efficiency. As a result of the comparison of MIM and conventional method in the analysis of samples in pharmacokinetic studies using model compounds, no difference was shown in the quantification values. Consequently, this method has some advantages, reduction of analytical time, the improvement of sensitivity, and the simplicity of system, compared to the conventional methods. MIM should be very useful and powerful method for drug development without an additional hardware and can be used for the measurement of compounds in biological samples for pharmacokinetic studies, especially it greatly contributes to accelerating drug development in its discovery stages.

Synthesis and activities of oxidative metabolites of the anti-arthritic drug candidate S-2474.

We have synthesized and characterized some oxidative metabolites of S-2474. In this study, we discovered a novel skeleton, the 2,3-dihydrobenzofuran derivative, which inhibited PGE(2) production at a very low concentration and was effective in the anti-carrageenin footpad edema assay.