Increases in bioavailability of poorly absorbed drug by acylcarnitine

Abstract

We examined the effect of acylcarnitines on the in situ bioavailability of lucifer yellow (LY) from the loops of small and large intestines of rats. The area under the blood concentration of LY versus time curve (AUC) from the jejunum was significantly increased by the treatments of the loop with 100 µM lauroylcarnitine (LC) or 100 µM palmitoylcarnitine (PC) (fourfold and 17‐fold, respectively). No marked change in the expression of claudin‐4 protein was observed by the treatments. On the contrary, the expression of P‐glycoprotein (P‐gp) was decreased by the treatment, more greatly by PC than by LC, suggesting that increases in the bioavailability of LY by LC and PC are associated with the decreased expression of P‐gp in jejunum. The increase in the bioavailability was also observed for colon by the treatment of LC, but not that of PC. LC decreased the expression of claudin‐4 protein, whereas PC decreased the expression of P‐gp in colon. Therefore, LC and PC appear to have different impact on the intestinal transporters depending on the site (i.e., jejunum and colon). © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci