Investigation on physicochemical and biological differences of cefpodoxime proxetil enantiomers.
Cefpodoxime proxetil (CP) is a prodrug of cefpodoxime acid (CA), and is supplied as racemic mixture of R- and S-enantiomers. CP has only 50% absolute bioavailability, and the reasons responsible for low bioavailability remain poorly understood. The present work ascertains physicochemical and biological properties of individual isomers of CP and explores their capacity to optimize delivery of CP. Both isomers showed similar pH stability behavior, but R-isomer was more susceptible to enzymatic metabolism compared to S-isomer, when incubated with enzymes collected from various segments of GIT. Based on the in vitro and in vivo results, use of S-isomer for development of a dosage form such as gastro-retentive dosage form can improve oral bioavailability of CP.
Kakumanu
Vasu Kumar
VK
Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India.
Arora
Vinod
V
Bansal
Arvind K
AK
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D015296:Ceftizoxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004355:Drug Stability; D041981:Gastrointestinal Tract / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008297:Male; D015394:Molecular Structure; D009904:Optical Rotation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014961:X-Ray Diffraction / Q000379:methods; D000097627:Cefpodoxime Proxetil
D000900:Anti-Bacterial Agents; D015296:Ceftizoxime; D000097627:Cefpodoxime Proxetil