Decanoic acid induced enhancement of rectal absorption of hydrophilic compounds in rats.
The enhancing effect of decanoic acid (C10) on the rectal absorption of phenolsulfonphtalein (PSP) was analyzed with a pharmacokinetic model. The transfer index of PSP from the rectal lumen to the epithelial layer in the presence of C10 was proportional to the product of the C10 disappearance rate from the rectal lumen and its calcium ion sequestration capacity. The enhancement of rectal PSP absorption by different doses of C10 was also predictable by using a permeability index, Pa, of PSP, which was defined as a proportionality constant relating transfer index and the product value described above. The Pa values of various hydrophilic compounds with different molecular weights were also estimated from their rectal bioavailability in the presence of C10. A linear relationship was observed between Pa values and reciprocal values of the square root of individual molecular weight. These findings suggest that the Pa index is related to the permeant's diffusion coefficient through paracellular aqueous openings formed by C10.
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
K
K
Takahashi
T
T
Murakami
R
R
Yumoto
T
T
Hattori
Y
Y
Higashi
N
N
Yata
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003652:Decanoic Acids / Q000494:pharmacology*; D004058:Diffusion; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008954:Models, Biological; D008970:Molecular Weight; D010539:Permeability; D010637:Phenolsulfonphthalein / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical
D003652:Decanoic Acids; C031071:decanoic acid; D010637:Phenolsulfonphthalein; D002118:Calcium