Stability of doripenem against human renal dehydropeptidase-I
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Accession number;05A0663315
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| Title;Stability of doripenem against human renal dehydropeptidase-I |
| Author;
YAMANO YOSHINORI
(Shionogi & Co., Ltd., JPN)
KAWAI YUI
(Shionogi & Co., Ltd., JPN)
YUTSUDO TAKASHI
(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.92-95(2005)
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| Figure&Table&Reference;FIG.2, REF.7 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;We evaluated the stability of doripenem, a novel carbapenem antibiotic, against human renal dehydropeptidase-I (DHP-I). Because imipenem, a carbapenem antibiotic, was reported to be easily hydrolyzed by human DHP-I, it is used in the clinic combined with DHP-I inhibitor cilastatin, so stability against human DHP-I plays an important roles in the human pharmacolanetics of carbapenem antibiotics. We evaluated stability against DHP-I using recombinant human renal DHP-I, purified by cilastatin-coupled affinity chromatography from COS-1 cells producing DHP-I. Purified DHP-I was shown to form a broad single band in SDS-polyacrylamide gel electrophoresis, suggesting that it was produced as a glycosylated protein in COS-1 cells. Stability was observed by determining the residual activity of the carbapenem antibiotics after incubation for 90 min in the presence of purified DHP-I. The residual activity of imipenem decreased with increasing activity of purified DHP-I. The residual activity of imipenem and meropenem after incubation with purified DHP-I was 20% and 80%, suggesting that meropenem, which is used without a DHP-I inhibitor in the clinic, is highly stable against DHP-I. Doripenem was as stable as meropenem under the same conditions, suggesting that doripenem and meropenem could be used without a DHP-I inhibitor in the clinic. (author abst.) |
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