Clinical Pharmacokinetics of Meropenem and Biapenem in Bile and Dosing Considerations for Biliary Tract Infections Based on Site-Specific Pharmacodynamic Target Attainment
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- Kazuro Ikawa
- Department of Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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- Akira Nakashima
- Department of Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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- Norifumi Morikawa
- Department of Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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- Kayo Ikeda
- Department of Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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- Yoshiaki Murakami
- Department of Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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- Hiroki Ohge
- Department of Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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- Hartmut Derendorf
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida
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- Taijiro Sueda
- Department of Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
Description
<jats:title>ABSTRACT</jats:title> <jats:p> The present study investigated the pharmacokinetics of meropenem and biapenem in bile and estimated their pharmacodynamic target attainment at the site. Meropenem (0.5 g) or biapenem (0.3 g) was administered to surgery patients ( <jats:italic>n</jats:italic> = 8 for each drug). Venous blood samples and hepatobiliary tract bile samples were obtained at the end of infusion (0.5 h) and for up to 5 h thereafter. Drug concentrations in plasma and bile were analyzed pharmacokinetically and used for a Monte Carlo simulation to predict the probability of attaining the pharmacodynamic target (40% of the time above the MIC). Both drugs penetrated similarly into bile, with mean bile/plasma ratios of 0.24 to 0.25 (maximum drug concentration) and 0.30 to 0.38 (area under the drug concentration-time curve). The usual regimens of meropenem (0.5 g every 8 h [q8h]) and biapenem (0.3 g q8h) (0.5-h infusions) achieved similar target attainment probabilities in bile (≥90%) against <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Escherichia coli</jats:named-content> , <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Klebsiella pneumoniae</jats:named-content> , and <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Enterobacter cloacae</jats:named-content> isolates. However, against <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Pseudomonas aeruginosa</jats:named-content> isolates, meropenem at 1 g q8h and biapenem at 0.6 g q8h were required for values of 80.7% and 71.9%, respectively. The biliary pharmacodynamic-based breakpoint (the highest MIC at which the target attainment probability in bile was ≥90%) was 1 mg/liter for 0.5 g q8h and 2 mg/liter for 1 g q8h for meropenem and 0.5 mg/liter for 0.3 g q8h and 1 mg/liter for 0.6 g q8h for biapenem. These results help to define the clinical pharmacokinetics of the two carbapenems in bile while also helping to rationalize and optimize the dosing regimens for biliary tract infections based on site-specific pharmacodynamic target attainment. </jats:p>
Journal
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- Antimicrobial Agents and Chemotherapy
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Antimicrobial Agents and Chemotherapy 55 (12), 5609-5615, 2011-12
American Society for Microbiology
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Details 詳細情報について
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- CRID
- 1362825894124139648
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- ISSN
- 10986596
- 00664804
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- Data Source
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- Crossref