Increases in bioavailability of poorly absorbed drug by acylcarnitine.
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).
Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan. tomita@toyaku.ac.jp
Mikio
M
Tomita
Nobuyuki
N
Doi
Aoi
A
Kimura
Masahiro
M
Hayashi
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D062506:Claudin-4 / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000187:drug effects*; D007546:Isoquinolines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007848:Laurates / Q000494:pharmacology*; D008297:Male; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D062506:Claudin-4; D005456:Fluorescent Dyes; D007546:Isoquinolines; D007848:Laurates; C116917:acylcarnitine; D010172:Palmitoylcarnitine; C091947:lauroylcarnitine; C017475:lucifer yellow; D007770:L-Lactate Dehydrogenase; D002331:Carnitine