Intestinal absorption of cephalexin in diabetes mellitus model rats.
We investigated the intestinal absorption and pharmacokinetics of cephalexin, as well as the intestinal H+/oligopeptide transporter PEPT1 mRNA and protein levels in type 1 and type 2 diabetic rats. Cephalexin disappearance from the duodenum loop was significantly lower in streptozotocin-induced type 1 diabetic rats and higher in hyperinsulinemic type 2 diabetic GK and Zucker-fa/fa (Zucker) rats, than in control rats. These results were speculated to be due to the enhancement of intestinal absorption of cephalexin in GK and Zucker rats. Intestinal PEPT1 mRNA levels were not significantly different between control and diabetic rats; however, the brush-border membrane vesicle PEPT1 protein levels were increased in GK and Zucker rats. After oral administration of cephalexin, plasma cephalexin concentrations and pharmacokinetic parameters, area under the concentration versus time curve from 0 to infinity, AUC(0-->infinity), and maximum plasma concentration, Cmax, in GK and Zucker rats were markedly higher than in control rats. From these findings, it is considered that intestinal absorption of drugs mediated by PEPT1 may be enhanced in hyperinsulinemic type 2 diabetes mellitus rats.
Watanabe
Kazuhiro
K
Hokkaido College of Pharmacy, 7-1 Katsuraoka-cho, Otaru, Hokkaido 047-0264, Japan. watanabe@hokuyakudai.ac.jp
Terada
Kazuaya
K
Sato
Juichi
J
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002506:Cephalexin / Q000097:blood / Q000493:pharmacokinetics*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004195:Disease Models, Animal; D007408:Intestinal Absorption / Q000502:physiology*; D008297:Male; D000074011:Peptide Transporter 1; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D027981:Symporters
D002352:Carrier Proteins; D000074011:Peptide Transporter 1; C489940:Slc15a1 protein, rat; D027981:Symporters; D002506:Cephalexin