Use of rabbits for GI drug absorption studies: relationship between dissolution rate and bioavailability of griseofulvin tablets.
The correlation between the dissolution rate and bioavailability of griseofulvin tablets was studied in stomach-emptying-controlled rabbits and in humans. Three different test tablets, each consisting of two dose levels (62.5 or 125 mg) of griseofulvin, were used. The dissolution rates in 0.5 hr were approximately 75, 40, and 12%. With oral administration at 62.5 mg/rabbit, the ratio of peak plasma level, Cmax, was 1.00:0.66:0.40 and that of the area under the curve (AUC) was 1.00:0.73:0.46 for the three tablets. The corresponding C'max ratio was 1.00:0.74:0.34 and the AUC ratio was 1.00:0.72:0.33 in humans at the dose level of 500 mg. A good correlation was observed for the rank order of Cmax and AUC between rabbits and humans, but such a correlation was not seen between in vivo data and in vitro data at a larger dose of 125 mg/rabbit. This finding was attributable to the dose, which exceeded the GI drug dissolution or absorption capacities. These results suggest that the stomach-emptying-controlled rabbit is useful for evaluating oral dosage forms for human use and that dose level selection is important in the bioavailability study of a barely water-soluble drug.
D000284:Administration, Oral; D000328:Adult; D000818:Animals; D001682:Biological Availability; D006118:Griseofulvin / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011817:Rabbits / Q000378:metabolism*; D012995:Solubility; D013607:Tablets; D013997:Time Factors
D004364:Pharmaceutical Preparations; D013607:Tablets; D006118:Griseofulvin