ENHANCED BIOAVAILABILITY OF CEFOXITIN USING PALMITOYLCARNITINE .2. USE OF DIRECTLY COMPRESSED TABLET FORMULATIONS IN THE RAT AND DOG

The performance of tablets containing the absorption enhancer palmitoy lcarnitine chloride (PCC) and the antibiotic cefoxitin (CEF) was deter mined by direct placement of tablets in the rat stomach, small intesti ne, 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 r at stomach. Following oral administration to dogs, tablets of 200 mg C EF without or with 600 mg PCC resulted in the same low bioavailabiliti es (7.0 +/- 10.3 and 7.0 +/- 3.6%, respectively). However, when these tablets were enteric coated, PCC improved CEF bioavailability from 2.4 4 +/- 1.84 to 29.0 +/- 13.4%. Therefore, the use of enteric-coated dir ect compressed tablets containing PCC and direct compression excipient s improved the peroral bioavailability of a poorly absorbed compound.