Acylcarnitines: drug absorption-enhancing agents in the gastrointestinal tract.
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.
D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002440:Cefoxitin / Q000378:metabolism; D003561:Cytarabine / Q000378:metabolism; D004285:Dogs; D005260:Female; D005839:Gentamicins / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000648:ultrastructure; D008297:Male; D008750:Methyldopa / Q000378:metabolism; D008854:Microscopy, Electron; D010172:Palmitoylcarnitine / Q000494:pharmacology; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012007:Rectum / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives / Q000378:metabolism
D005839:Gentamicins; D004364:Pharmaceutical Preparations; D003561:Cytarabine; D010172:Palmitoylcarnitine; D013004:Somatostatin; D008750:Methyldopa; D002440:Cefoxitin; D002331:Carnitine