Abstract
The enhancing action of decanoic acid (C1O) 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.
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REFERENCES
N. Yata, Y. Higashi, T. Murakami, R. Yamajo, W. M. Wu, K. Taku, Y. Sasaki, and Y. Hideshima. A possible mechanism of absorption promoters. J. Pharmacobio-Dyn. 6:s-78 (1983).
T. Murakami, M. Kishimoto, H. Kawakita, M. Misaki, Y. Kojima, Y. Higashi, H. Amagase, T. Fuwa, and N. Yata. Enhanced rectal and nasal absorption of human epidermal growth factor by combined use of the absorption promoter and the synthetic polymer in rats. Eur. J. Drug Metab. Pharmacokin. Spec. Iss. 4:125–131 (1991).
T. Murakami, Y. Sasaki, R. Yamajo, and N. Yata. Effect of bile salts on the rectal absorption of sodium ampicillin in rats. Chem. Pharm. Bull. 32:1948–1955 (1984).
K. Sakai, T. Matsuura, T. Nishino, Y. Fujihara, and N. Yata. Contribution of calcium ion sequestration by polyoxyethylated nonionic surfactants to the enhanced colonic absorption of p-aminobenzoic acid. J. Pharm. Sci. 75:387–390 (1986).
W. M. Wu, T. Murakami, R. Yamajo, Y. Higashi, and N. Yata. Calcium ion sequestration by N-acylamino acids within the rectal membrane and the enhancement of the rectal absorption of sodium ampicillin in rats. J. Pharm. Sci. 78:499–503 (1989).
K. Yamaoka and T. Nakagawa. A nonlinear least squares program based on differential equations, MULTI(RUNGE), for microcomputers. Pharmacobio-Dyn. 6:595–606 (1983).
M. M. Cassidy and C. S. Tidball. Cellular mechanism of intestinal permeability alterations produced by chelation depletion. J. Cell Biol. 32:685–698 (1967).
M. Tomita, M. Hayashi, T. Horie, T. Ishizawa, and S. Awazu. Enhancement of colonic drug absorption by transcellular permeation route. Pharm. Res. 5:786–789 (1988).
M. Tomita, M. Shiga, M. Hayashi, and S. Awazu. Enhancement of colonic drug absorption by the paracellular permeation route. Pharm. Res. 5:341–346 (1988).
J. H. Hunt and P. R. Mchugh. Dose calcium mediate the slowing of gastric emptying in primates. Am. J. Physiol. 243:G200–G203 (1982).
M. Takeichi. Cadherin cell adhension receptors as a morphogenetic regulator. Science 251:1451–1455 (1991).
A. Nagafuchi, Y. Shirayoshi, K. Okazaki, K. Yasuda, and M. Takeichi. Transformation of cell adhension properties by exogenously introduced E-cadherin cDNA. Nature 329:341–343 (1987).
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Takahashi, K., Murakami, T., Kamata, A. et al. Pharmacokinetic Analysis of the Absorption Enhancing Action of Decanoic Acid and Its Derivatives in Rats. Pharm Res 11, 388–392 (1994). https://doi.org/10.1023/A:1018908903475
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DOI: https://doi.org/10.1023/A:1018908903475