Enhanced bioavailability of cefoxitin using palmitoylcarnitine. II. Use of directly compressed tablet formulations in the rat and dog.
The performance of tablets containing the absorption enhancer palmitoylcarnitine chloride (PCC) and the antibiotic cefoxitin (CEF) was determined by direct placement of tablets in the rat stomach, small intestine, and colon. While the bioavailability (F) of tablets containing 12 mg CEF without PCC ranged from 0.6 to 3.9%, the addition of 24 mg PCC resulted in an enhanced CEF bioavailability in the rat colon (mean +/- SD: F = 57 +/- 19%) and rat jejunum (F = 71 +/- 16%) but not in the rat stomach. Following oral administration to dogs, tablets of 200 mg CEF without or with 600 mg PCC resulted in the same low bioavailabilities (7.0 +/- 10.3 and 7.0 +/- 3.6%, respectively). However, when these tablets were enteric coated, PCC improved CEF bioavailability from 2.44 +/- 1.84 to 29.0 +/- 13.4%. Therefore, the use of enteric-coated direct compressed tablets containing PCC and direct compression excipients improved the peroral bioavailability of a poorly absorbed compound.
Sutton
S C
SC
INTERx Research Corporation, Lawrence, Kansas 66047.
LeCluyse
E L
EL
Engle
K
K
Pipkin
J D
JD
Fix
J A
JA
D000818:Animals; D001682:Biological Availability; D002440:Cefoxitin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004285:Dogs; D004337:Drug Carriers; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007583:Jejunum; D008297:Male; D010172:Palmitoylcarnitine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach; D013608:Tablets, Enteric-Coated
D004337:Drug Carriers; D013608:Tablets, Enteric-Coated; D010172:Palmitoylcarnitine; D002440:Cefoxitin