Improvement of bioavailability of poorly absorbed drugs. II. Effect of medium chain glyceride base on the intestinal absorption of cefmetazole sodium in rats and dogs.
The effect of medium chain glyceride (MCG) on the intestinal absorption of cefmetazole sodium (CMZ) was investigated in rats and dogs. In rats, MCG containing glyceryl mono-, di- and tri-caprylate enhanced the intestinal absorption of CMZ after intraduodenal administration, though the promoting effect of MCG was less than that after rectal administration. The promoting effect of MCG was found to be mainly due to glycerylmonocaprylate and dependent on the dosage of MCG. The plasma CMZ levels after intraduodenal administration as MCG solution tended to be slightly higher than those observed after administration as MCG emulsion, though the differences were found to be statistically insignificant. Moreover, the intestinal absorption of CMZ after intraduodenal administration as MCG emulsion was decreased significantly by increasing the amount of water in the emulsion. The promoting effect of MCG in dogs was more clearly demonstrated in the lower intestine than in the upper intestine. Furthermore, the oral bioavailability of pharmaceutical formulations of CMZ was also investigated in dogs. When enteric coated capsules filled with MCG solution were administered to dogs, the bioavailability of CMZ was enhanced significantly.
D000818:Animals; D001682:Biological Availability; D015311:Cefmetazole; D002513:Cephamycins / Q000008:administration & dosage / Q000378:metabolism*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005989:Glycerides / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002513:Cephamycins; D005989:Glycerides; D015311:Cefmetazole