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In vitro permeation of β‐lactam antibiotics across rat jejunum and its correlation with oral bioavailability in humans
Author(s) -
Saitoh Hiroshi,
Aungst Bruce J.,
Tohyama Masashi,
Hatakeyama Yuko,
Ohwada Keiko,
Kobayashi Michiya,
Fujisaki Hiroko,
Miyazaki Katsumi
Publication year - 2002
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2002.t01-1-01672.x
Subject(s) - bioavailability , permeation , jejunum , chemistry , intestinal permeability , pharmacokinetics , pharmacology , in vitro , penetration (warfare) , chromatography , biochemistry , medicine , operations research , membrane , engineering
AimsTo investigate the correlation between in vitro permeation of 11 β‐lactam antibiotics across rat jejunum and their oral bioavailability in humans.MethodsThe absorptive and secretory permeation across rat jejunum was evaluated and apparent permeability coefficients (P app ) were determined.ResultsA 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.ConclusionsFor 11 β‐lactam antibiotics rat intestinal permeation correlated well with human oral bioavailability, especially when corrected for secretory transport.