Absorption enhancement of rectally infused cefoxitin by medium chain monoglycerides in conscious rats.
The enhancing effect of the medium chain monoglycerides glyceryl-1-monoctanoate (GMO), glyceryl-1-monodecanoate (GMD), and glyceryl-1-monododecanoate (GMDD) on rectal absorption of the cephalosporin antibiotic cefoxitin [(6R,7S)-3-hydroxymethyl)-7-methoxy-8-oxo-7-[2-(2-thienyl)acetamido]-5- thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid carbamate (ester)] was investigated in unanesthetized rats. Rectal infusion of 3 mg of cefoxitin sodium without monoglyceride resulted in a mean bioavailability of 31 +/- 18% and a mean residence time (MRT) of 134 +/- 44 min. Coadministration with 53% (w/w) GMO significantly enhanced cefoxitin absorption, resulting in a mean bioavailability of 84 +/- 11% and a mean MRT of 75 +/- 8 min. In a lower concentration, GMD (13% w/w) also significantly promoted cefoxitin bioavailability to 68 +/- 14% and reduced MRT to 70 +/- 11 min. With GMDD only, a trend of increasing bioavailability with increasing monoglyceride concentration was observed, which may be explained by its limited aqueous solubility. Concerning the action of GMO and GMD, the longer monoglyceride is, in terms of effective concentration, more potent in enhancing the extent and rate of cefoxitin absorption. However, a further increase in chain length results in a loss of effect, indicating that the effect of monoglycerides on drug absorption may be determined by their intrinsic absorption enhancing action and solubility.
Watanabe
Y
Y
Bio-Pharmaceutical Sciences, Sylvius Labs, Leiden University, The Netherlands.
van Hoogdalem
E J
EJ
de Boer
A G
AG
Breimer
D D
DD
D000285:Administration, Rectal; D000818:Animals; D002440:Cefoxitin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005989:Glycerides / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D005989:Glycerides; D002440:Cefoxitin