title: In vitro permeation of beta-lactam antibiotics across rat jejunum and its correlation with oral bioavailability in humans.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan. saitoh@hoku.iryo-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saitoh
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Aungst
authors.forename: Masashi
authors.initials: M
authors.lastname: Tohyama
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hatakeyama
authors.forename: Keiko
authors.initials: K
authors.lastname: Ohwada
authors.forename: Michiya
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Fujisaki
authors.forename: Katsumi
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006033:Glycylglycine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000502:physiology; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D006033:Glycylglycine