AJP - Gastrointestinal and Liver Physiology, Vol 251, Issue 3 332-G340, Copyright © 1986 by American Physiological Society
Acylcarnitines: drug absorption-enhancing agents in the gastrointestinal tract
J. A. Fix, K. Engle, P. A. Porter, P. S. Leppert, S. J. Selk, C. R. Gardner and J. Alexander
Acylcarnitines were tested as potential absorption-enhancing agents for
drugs that are poorly absorbed from the gastrointestinal tract.
Urethan-anesthetized Sprague-Dawley rats and conscious Beagle dogs were
used. Palmitoyl-DL-carnitine was the most effective acylcarnitine tested,
although significant increases in drug absorption were observed with
acylcarnitines containing C12 through C18 fatty acid chains.
Palmitoyl-DL-carnitine afforded significant increases in the absorption of
cefoxitin, gentamicin, cytarabine, somatostatin analogue, and
alpha-methyldopa. The response to palmitoyl-DL-carnitine was concentration
dependent and reversible within 60-120 min. Histological examination of the
intestinal tissue revealed no apparent change in mucosal structural
integrity at doses of palmitoyl-DL-carnitine that resulted in increased
drug absorption. The acylcarnitines were effective in increasing drug
absorption from the small intestine and the rectal compartment of both rats
and dogs. The data also demonstrated effectiveness with aqueous and solid
dosage forms (Witepsol H-15 suppositories). The data suggest that
acylcarnitines may be effective and safe absorption-enhancing agents for a
variety of drugs.
