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  • Title: In vitro permeation of beta-lactam antibiotics across rat jejunum and its correlation with oral bioavailability in humans.
    Author: Saitoh H, Aungst BJ, Tohyama M, Hatakeyama Y, Ohwada K, Kobayashi M, Fujisaki H, Miyazaki K.
    Journal: Br J Clin Pharmacol; 2002 Oct; 54(4):445-8. PubMed ID: 12392595.
    Abstract:
    AIMS: To investigate the correlation between in vitro permeation of 11 beta-lactam antibiotics across rat jejunum and their oral bioavailability in humans. METHODS: The absorptive and secretory permeation across rat jejunum was evaluated and apparent permeability coefficients (P(app)) were determined. RESULTS: A steep, sigmoid-type curve was obtained for the relationship between P(app) in the absorptive permeation and human oral bioavailability. When the ratios of P(app) in the absorptive direction to P(app) in the secretory direction were plotted against human oral bioavailability, a much improved correlation was obtained (r = 0.98, P < 0.001). The addition of glycylglycine to both mucosal and serosal media modified the permeation of ceftibuten and cephalexin from the absorptive to the secretory direction. CONCLUSIONS: For 11 beta-lactam antibiotics rat intestinal permeation correlated well with human oral bioavailability, especially when corrected for secretory transport.
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