Investigation of factors responsible for low oral bioavailability of cefpodoxime proxetil.
Learning about the behavior of a drug in biological environment enables application of better formulation strategies to improve bioavailability of the same. Cefpodoxime proxetil (CP) is a prodrug, which is orally administered cephalosporin with only 50% absolute bioavailability. Despite previous studies, reasons responsible for low bioavailability of CP remain poorly understood. The present study tries to ascertain reasons for the low oral bioavailability of CP. The in vitro, in situ and ex vivo studies showed interesting results, where metabolism of CP into cefpodoxime acid (CA) inside the intestinal epithelial cell and preferential efflux of CA into lumen was identified as primary reason for low oral bioavailability of CP. Presence of specific carriers or transportation mechanism on the apical side membrane of enterocyte, than basal side of the same was observed.
Kakumanu
Vasu Kumar
VK
Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, Phase X, SAS Nagar, Punjab 160 062, India.
Arora
Vinod
V
Bansal
Arvind K
AK
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D015296:Ceftizoxime / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D020895:Enterocytes / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007583:Jejunum / Q000201:enzymology / Q000378:metabolism; D008297:Male; D011355:Prodrugs / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097627:Cefpodoxime Proxetil
D000900:Anti-Bacterial Agents; D015296:Ceftizoxime; D011355:Prodrugs; D000097627:Cefpodoxime Proxetil