Pharmacokinetic analysis of the absorption enhancing action of decanoic acid and its derivatives in rats.
The enhancing action of decanoic acid (C10) and its derivatives on mucosal absorption of phenolsulfonphthalein (PSP) in the jejunum or colon was analyzed using pharmacokinetics in rats. After administration of a solution containing PSP and an enhancer [C10, 2-hydroxydecanoic acid (2-OHC10), or 3-hydroxydecanoic acid (3-OHC10)] into the jejunal or colonic loop, the amounts of PSP and enhancer remaining in the loop and/or plasma PSP concentration were determined periodically. 2-OHC10 exhibited a greater absorption enhancing potency than C10, while 3-OHC10 was less effective. Disappearance of residual PSP from the loop ceased after complete absorption of the enhancer. The enhancer-induced disappearance rate constant of PSP correlated well with the product of the enhancer disappearance rate and its capacity to sequester calcium ions. In conclusion, the enhancement of PSP mucosal absorption by C10 and its derivatives is consistent with a pharmacokinetic model, assuming that the enhanced membrane permeability of PSP depends on the enhancer disappearance kinetics from the loop and its calcium ion sequestration capacity.
Takahashi
K
K
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
Murakami
T
T
Kamata
A
A
Yumoto
R
R
Higashi
Y
Y
Yata
N
N
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003651:Decanoates / Q000494:pharmacology; D003652:Decanoic Acids / Q000494:pharmacology*; D004395:Dye Dilution Technique; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D010637:Phenolsulfonphthalein / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical
D003651:Decanoates; D003652:Decanoic Acids; C031071:decanoic acid; C024706:2-hydroxydecanoic acid; D010637:Phenolsulfonphthalein; C017552:myrmicacin; D002118:Calcium