Therapeutic efficacy of doripenem, a novel parenteral carbapenem antibiotic, against experimental infection in mice and rats
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Accession number;05A0663313
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| Title;Therapeutic efficacy of doripenem, a novel parenteral carbapenem antibiotic, against experimental infection in mice and rats |
| Author;
SATO TAKAFUMI
(Shionogi & Co., Ltd., JPN)
TSUJI MASAKATSU
(Shionogi & Co., Ltd., JPN)
OKAZAKI KEN'ICHI
(Shionogi & Co., Ltd., JPN)
MATSUDA HAYATO
(Shionogi & Co., Ltd., JPN)
YOSHITOMI TORIKO
(Shionogi & Co., Ltd., JPN)
MIWA HIDEAKI
(Shionogi & Co., Ltd., JPN)
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Journal Title;Japanese Journal of Chemotherapy
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Journal Code:F0608A
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ISSN:1340-7007
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VOL.53;NO.Supplement 1;PAGE.71-79(2005)
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| Figure&Table&Reference;FIG.2, TBL.5, REF.13 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;The in vivo antibacterial efficacy of doripenem (DRPM), a new parenteral carbapenem antibiotic, was compared to that of meropenem/cilastatin (MEPM/CS), imipenem/cilastatin (IPM/CS), ceftazidime (CAZ), and ampicillin (ABPC) against experunental infection in mice and rats. Compared to a single administration of DRPM in mice, plasma concentration of DRPM with administration combined with CS (DRPM: CS=1:1) did not improve, but plasma concentration of DRPM in rats was improved by combination with CS. No difference was seen in pharmacokinetic properties of plasma among DRPM, MEPM/CS, and IPM/CS in mice and among DRPM/CS, MEPM/CS, and IPM/CS in rats. Against marine systemic infection caused by gram-positive bacteria including penicillin-resistant Streptococcus pneumoniae (PRSP), DRPM exhibited good efficacy with ED50 of 0.02-6.26 mg/kg, superior to MEPM/CS, CAZ, and ABPC but inferior to IPM/CS. DRPM also showed potent efficacy (ED50s: 0.04-2.49 mg/kg) against gram-negative bacterial infection including CAZ-resistant Enterobacter cloacae and was more active than IPM/CS, but less active than MEPM/CS. In a mouse lung infection model caused by PRSP, DRPM caused significant reduction of viable cells in the lung at 3 mg/kg or more, though ABPC was not effective at 10 mg/kg. The therapeutic efficacy of DRPM was more active significantly than that of ABPC and CAZ and similar to that of MEPM/CS, but inferior to that of IPM/CS. In rat meningitis caused by PRSP, DRPM/CS caused significant reduction of viable cells in cerebrospinal fluid at 10 mg/kg or more than. DRPM was more active than ABPC, CAZ, and MEPM/CS, but less active than IPM/CS. In a rat endocarditis model caused by Staphylococcus aureus, DRPM showed excellent efficacy with significant reduction of viable cells in the heart at 4 mg/kg or more. Its efficacy was more potent than that of CAZ and MEPM/CS and was comparable to that of IPM/CS.... (author abst.) |
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