The enhancing mechanism of capric acid (C10) from a suppository on rectal drug absorption through a paracellular pathway.
Capric acid (C10) enhanced the absorption of cefoxitin sodium in a concentration-dependent manner following the rectal administration as a suppository in rats. The optimal concentration of C10 was 13%. C10 administered as a suppository also reduced rectal membrane resistance (Rm), showing that the above enhancing effect was induced by widening the paracellular pathway. Both the enhancing effect on the absorption and the reducing effect on Rm were inhibited by W7, an inhibitor of myosin light chain kinase. These results supported that, as shown in the in vitro Caco-2 cell system, the C10 effect on the paracellular pathway is due to activating the contraction of Ca(2+)-calmodulin-dependent actin filament.
Takahashi
H
H
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Shibasaki
T
T
Takeshita
K
K
Kaiho
F
F
Hayashi
M
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000285:Administration, Rectal; D000818:Animals; D002440:Cefoxitin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002513:Cephamycins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003652:Decanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum / Q000187:drug effects* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D013488:Suppositories
D002513:Cephamycins; D003652:Decanoic Acids; D013449:Sulfonamides; D013488:Suppositories; C017967:W 7; D002440:Cefoxitin; C080501:1-(5-isoquinolinylsulfonyl)-3-methylpiperazine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase