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Antimicrobial Agents and Chemotherapy, July 2009, p. 2799-2803, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.01578-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Comparison of the Pharmacodynamics of Biapenem in Bronchial Epithelial Lining Fluid in Healthy Volunteers Given Half-Hour and Three-Hour Intravenous Infusions{triangledown}

Eiki Kikuchi,1* Junko Kikuchi,1 Yasuyuki Nasuhara,1 Satoshi Oizumi,1 Akitoshi Ishizaka,2 and Masaharu Nishimura1

First Department of Medicine, Hokkaido University School of Medicine, North 15, West 7, Kitaku, Sapporo 0608638,1 Department of Medicine, Keio University School of Medicine, 35, Shinano-machi, Shinjuku-ku, Tokyo 1608582, Japan2

Received 27 November 2008/ Returned for modification 8 February 2009/ Accepted 9 April 2009

The time above the MIC (T>MIC) is the pharmacokinetic/pharmacodynamic (PK/PD) parameter that correlates with the therapeutic efficacy of beta-lactam antibiotics. A prolonged infusion can provide plasma drug concentrations that remain above the MIC for a long period. The objective of this study was to compare the PK/PD parameters in bronchial epithelial lining fluid (ELF) of biapenem given as 0.5-h and 3-h infusions by using bronchoscopic microsampling (BMS). Six healthy adult volunteers received 0.5-h and 3-h infusions of 0.3 g of biapenem with a washout interval. BMS was performed repeatedly from 0.5 to 24 h after biapenem administration in order to determine the pharmacokinetics in bronchial ELF. The subjects received intravenous biapenem with the same regimens again and then underwent bronchoalveolar lavage (BAL) at the end of infusion in order to determine the concentration of the drug in alveolar ELF. The percentages (means ± standard deviations) of T>MIC in bronchial ELF at MICs from 0.25 to 4 µg/ml ranged from zero to 34.6% ± 5.2% after the 0.5-h infusion and from 5.1% ± 5.6% to 52.2% ± 17.0% after the 3-h infusion. The percentage of T>MIC in bronchial ELF after the 3-h infusion tended to be higher than that after the 0.5-h infusion. The concentrations of the drug in alveolar ELF after 0.5-h and 3-h infusions were 3.5 ± 1.2 µg/ml and 1.3 ± 0.3 µg/ml, respectively. The present results support the use of prolonged infusions of beta-lactam antibiotics and may provide critical information for successful treatment of lower respiratory tract infections based on PK/PD parameters in bronchial ELF.

* Corresponding author. Mailing address: First Department of Medicine, Hokkaido University School of Medicine, North 15, West 7, Kitaku, Sapporo 060-8638, Japan. Phone: 81-11-706-5911. Fax: 81-11-706-7899. E-mail: eikik{at}med.hokudai.ac.jp

{triangledown} Published ahead of print on 20 April 2009.

Antimicrobial Agents and Chemotherapy, July 2009, p. 2799-2803, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.01578-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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