In-vitro and in-vivo studies of cefpirom using bile salts as absorption enhancers.
Cephalosporins have to be administered by injection because of the poor intestinal absorption of the orally delivered drugs. Because of the obvious drawbacks of drug delivery by injection, the development of alternatives with enhanced oral bioavailability is receiving much attention in pharmaceutical research. Cefpirom (Cp) is a new semi-synthetic amino-2-thiazolyl-methoxyimino cephalosporin that has been substituted in position 3 with a cyclopenteno-pyridinium group in order to create a zwitterionic compound. It exhibits highly hydrophilic properties, as shown from its extremely low partition coefficient, and therefore its lipophilicity was increased using bile salts. The effect of this on the partition coefficients determined in the n-octanol/buffer system was confirmed using an in-vitro transport model with artificial and biological membranes. The pharmacokinetic properties of Cp were investigated in rabbits after intraduodenal administration with and without bile salts. Furthermore, the physiological compatibility of the bile salts was investigated using active D-glucose transport.
Mrestani
Yahya
Y
Institute of Pharmaceutics and Biopharmaceutics, Department of Pharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle, Germany.
Bretschneider
Beate
B
Härtl
Albert
A
Neubert
Reinhard H H
RH
D000818:Animals; D019540:Area Under Curve; D001647:Bile Acids and Salts / Q000494:pharmacology*; D001682:Biological Availability; D001692:Biological Transport / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002511:Cephalosporins / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005947:Glucose / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D008954:Models, Biological; D011817:Rabbits; D000097572:Cefpirome
D001647:Bile Acids and Salts; D002511:Cephalosporins; D005947:Glucose; D000097572:Cefpirome