Influence of enhancers on the absorption and on the pharmacokinetics of cefodizime using in-vitro and in-vivo models

Abstract

In the development of novel antibiotics, more and more compounds have been found that cannot be absorbed orally and, therefore, must be administered intravenously or intramuscularly. Because of the obvious drawbacks of drug delivery by injection, the development of alternatives with enhanced oral bioavailability has received much attention in pharmaceutical research. Cefodizime, a novel third-generation cephalosporin with significant advantages in the parenteral treatment of common infections, was used as a model drug. Cefodizime behaves as a highly hydrophilic compound, as shown from its extremely low partition coefficient. The effect of cationic absorption enhancers (hexadecyldimethylbenzylammonium chloride, N-hexadecylpyridinium bromide, dodecyltrimethylammonium bromide and hexadecyltrimethylammonium bromide) on the lipophilicity of cefodizime was investigated by means of the n-octanol/water system. Results showed that the counter-ions had a positive influence on the solubility of cefodizime. These results on partitioning coefficients in the n-octanol/buffer system were confirmed using an in-vitro transport model with artificial and biological membranes (Caco-2-cells). Furthermore, the physiological compatibility of the absorption enhancers was investigated using the active D-glucose transport. The pharmacokinetic profile of cefodizime was evaluated in rabbits after intraduodenal administration with and without an absorption enhancer.

Enhanced Antibacterial Effect of Ceftriaxone Sodium-Loaded Chitosan Nanoparticles Against Intracellular Salmonella typhimurium

“…Moreover, it showed clinical failure in treating salmonellosis (10). The poor cellular penetration of the antibiotic was attributed to its high molecular weight (661.6) as well as its hydrophilicity (log P −0.6) (11)(12)(13)(14)(15)(16). Efforts have been made to increase its oral absorption.…”

Design and synthesis of a series of novel, cationic liposaccharide derivatives as potential penetration enhancers for oral drug delivery

“…[24][25][26] Measurements of CAC also provide some insights into the potential toxicity of the designed penetration enhancers, notably likelihood to cause disruptions to biological membranes due to their surfactant properties. 27,28 A number of quantification methods of the critical micellar concentration (CMC) of ionic or non-ionic surfactants in aqueous systems have been reported.…”