Absorption-enhancing effect of glycyrrhizin induced in the presence of capric acid.
The absorption-enhancing effect of the simultaneous administration of sodium caprate (Cap-Na) and dipotassium glycyrrhizinate (Grz-K) was investigated to clarify an effect of Grz-K. A combination of 0.1% (w/v) Cap-Na and 2% (w/v) Grz-K had a rapid and long-lasting absorption-enhancing activity in Caco-2 cell monolayers under conditions where Cap-Na and Grz-K showed a weak and no activity, respectively. The simultaneous treatment of a Caco-2 cell monolayer with Cap-Na and Grz-K showed no change in intracellular calcium ion level, although a major mechanism of absorption-enhancing effect for Cap-Na was elevation of intracellular calcium ion level. On the other hand, the simultaneous enhancing effect of Cap-Na and Grz-K was inhibited by H7, a PKC inhibitor. Possibly, Grz-K showed an absorption-enhancing effect via PKC cellular signaling pathway after penetration into cell according to increasing membrane permeability by Cap-Na. The absorption of sCT by the rat colon was enhanced by a combination of 0.1% (w/v) Cap-Na and 2% (w/v) Grz-K, and its effect continued even 9h after the onset of the experiment. Furthermore, the simultaneous treatment of 0.1% (w/v) Cap-Na and 2% (w/v) Grz-K showed a negligible histological changes to the colon mucosal membrane and a negligible toxicity on Caco-2 cell monolayer. A combination of Cap-Na and Grz-K shows a synergistic absorption-enhancing effect with little mucosal injury, which is applicable to colon-specific delivery.
Imai
Teruko
T
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan. iteruko@gpo.kumamoto-u.ac.jp
Sakai
Michinori
M
Ohtake
Hiroshi
H
Azuma
Hidekazu
H
Otagiri
Masaki
M
D000042:Absorption / Q000187:drug effects / Q000502:physiology; D000818:Animals; D018938:Caco-2 Cells; D003652:Decanoic Acids / Q000493:pharmacokinetics*; D004347:Drug Interactions; D019695:Glycyrrhizic Acid / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D003652:Decanoic Acids; C031071:decanoic acid; D019695:Glycyrrhizic Acid