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Pharmacokinetics and bioavailability of oral cephalosporins, KR-984055 and its prodrugs, KR-999001 and KR-999002, in the rat

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Abstract

KR-984055 is a new oral cephalosporin antibiotic with activity against both gram-positive and gram-negative bacteria. Lipophilic ester-type prodrugs of KR-984055, i.e., KR-999001 and KR999002, have been synthesized in an attempt to increase the oral bioavailability of this broadspectrum antibiotic agent. In this study we determined the oral bioavailability of KR-984055 and its prodrugs in the rat, and evaluated the pharmacokinetic model that best describes the plasma concentration behavior following single intravenous (IV) and oral single dose. In addition, concentrations in plasma as well as biliary and urinary recovery of KR-984055 were determined. Also, protein binding of KR-984055 in plasma was examinedin vitro. The degree of protein binding of KR-984055was in the range of 92.09∼94.77%. KR-984055 exhibited poor oral bioavailability (7.02 ± 1.58%). The observed oral bioavailabilities of KR-984055 from KR999001 and KR-999002 were 38.77± 2.81% and 39.81 ± 5.25%, respectively. These data were calculated from the levels of free KR-984055 in plasma. Oral KR-999001 and KR-999002 were not recovered from plasma, suggesting that it was readily cleaved to free KR-984055. KR999001 and KR-999002 appear to be an efficient oral prodrug of KR-984055 that deserved further clinical evaluation in human.

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Authors and Affiliations

  1. Korea Research Institute of Chemical Technology, 305-343, Daejeon, Korea

    Myung Hee Jung

  2. College of Pharmacy, Chungnam National University, 305-764, Daejeon, Korea

    Yong Soon Park, Su Kyung Woo & Kwang-il Kwon

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  1. Yong Soon Park
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  2. Su Kyung Woo
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  3. Myung Hee Jung
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  4. Kwang-il Kwon
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Correspondence to Kwang-il Kwon.

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Park, Y.S., Woo, S.K., Jung, M.H. et al. Pharmacokinetics and bioavailability of oral cephalosporins, KR-984055 and its prodrugs, KR-999001 and KR-999002, in the rat. Arch Pharm Res 26, 83–88 (2003). https://doi.org/10.1007/BF03179937

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  • DOI: https://doi.org/10.1007/BF03179937

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