PHARMACOKINETIC STUDY OF PENETRATION OFMEROPENEM INTO PLEURAL EFFUSION IN PATIENTS WITH PLEURISY

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  • 胸膜炎患者におけるMeropenemの胸水移行に関する薬物動態学的検討

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Abstract

Complication by secondary infection is observed in not only bacterial pleurisy but also other pleurisy, and the appropriate administration of antibacterial agents is necessary. It is very important to secure a smooth penetration of systemically administered antibacterial agents to pleural effusion in infection therapy. In this study, we investigated the pharmacokinetics of a carbapenem antibiotic, meropenem (MEPM), in blood and pleural effusion in patients with an accumulation of pleural effusion caused by pleurisy, who underwent placement of an indwelling thoracic drain and received intravenous drip administration of MEPM for pneumonia or other respira- tory tract infection. The blood pharmacokinetic parameters of MEPM after an intravenous drip administration of 0.5 g MEPM in six patients were: area under the blood concentration-time curve (AUC∞), 37.9±6.2 (hr.mg/L); volume of distribution (Vd), 27.3±4.4 (L); total clearance (CLtotal), 13.4±1.8 (L/hr); elimination half life (t1/2), 0.50±0.08 (hr-1); and elimination rate constant (kel), 1.42±0.22 (hr). The pharmacokinetic parameters in pleural effusion were: AUC∞, 35.7±7.1 (hr. mg/L); mean retention time (MRT), 5.00±3.25 (hr); variance of retention time (VRT), 29.9±44.6 (hr2); kel, 0.34±0.27 (hr-1); and t1/2, 3.14±2.36 (hr). The penetration rate calculated from the ratio of pleural concentration to blood concentration in each patient was 46.5±26.1%, showing good penetra- tion comparable or superior to those of other antibacterial agents previously reported. From these results, it was suggested that MEPM was rapidly penetrated to the pleural effusion and was retained for a more prolonged time in the pleural effusion than in the blood of patients with accumulated pleural effusion, and it suggested the useful- ness of MEPM in antibacterial therapy for patients with pleurisy causing accumulation of pleural effusion.

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