Transport of cephalosporins across artificial membranes and rabbit ileum

• Published in: International journal of pharmaceutics Vol. 145; no. 1; pp. 115 - 127
• Main Authors: Benkhelifa, Samir, Decroix, Maric-O., Arnaud, Philippe, Huneau, Jean-F., Tomé, Daniel, Chaumeil, Jean-C.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 06.12.1996; Elsevier
• Subjects: Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Artificial membranes; Biological and medical sciences; Epithelial transport; Life Sciences; Medical sciences; Michaelis-Menten kinetic; Passive diffusion; pH-dependence; Pharmacology. Drug treatments; α-amino group; Passive diffusion; Epithelial transport; Michaelis-Menten kinetic; Artificial membranes; α-amino group; pH-dependence; Cefalexin; Digestive system; Biological transport; Gut; Rabbit; Artificial membrane; Biomembrane; Concentration; Lagomorpha; Ileum; In vitro; Vertebrata; Antibiotic; Cephalosporin derivatives; Mammalia; Animal; pH; Models; Kinetics; Cefadroxil; Antibacterial agent; Cefaclor; Transepithelial transport; TRANSPORT TRANS-EPITHELIAL
• DOI: 10.1016/S0378-5173(96)04743-6
• ISSN: 0378-5173

The aim of this study is to determine transepithelial transport of aminocephalosporins (cephalexin, cefaclor and cefadroxil) with in vitro models using artificial and biological membranes. The three antibiotics have higher partition coefficient ( K p) at pH 5 than at pH 6 and cephalexin passes through the lipid barrier faster than cefadroxil and cefaclor. With a cephalexin concentration of 1 mM, the diffusion rate constant ( K d) through the artificial intestinal barrier was 0.563 ± 0.001 and 0.426 ± 0.031 ( × 10 −3 cm/ min) at pH 5 and 6, respectively. The transepithelial passage of the three aminocephalosporins through rabbit ileum tissues is measured in an Ussing chamber. The mean transepithelial mucosal to serosal fluxes ( Φ m-s) were 52.54 ± 6.45 nmol/h/cm 2 and 27.51 ± 2.43 nmol/h/cm 2 for cephalexin and cefadroxil, respectively. No effect on intensity short-circuit ( I sc) and conductance ( G) of the tissue were observed with cephalexin. In Grass cell diffusion with pH ranged from 6 to 7.4, showed a maximal cephalexin transport at pH 6. The concentration dependence of cephalexin absorption and transport was examined over a concentration range of 0.1–5 mM. The cephalexin transport involves Michaelis-Menten kinetics. Moreover, D-glucose does not affect the cephalexin (CFX) flux across the ileal tissue.