The in vitro liberation and the bioavailability of different brands of griseofulvin in plasma and urine in man
Terhaag, B.; Le Petit, G.; Pachaly, C.; Feller, K.
International Journal of Clinical Pharmacology Therapy and Toxicology 23(9): 475-479
1985
ISSN/ISBN: 0174-4879 PMID: 4055158 Document Number: 247821
The bioavailability of griseofulvin in three different brands, two microfine forms (Gricin = G, Likuden = L), and one ultramicrofine form (Gris-PEG = GP), was determined in plasma and urine in six healthy volunteers in a crossover study and compared with in vitro liberation data. GP shows a higher AUC.infin.0 (140 .+-. 24 .mu.mol .cntdot. h .cntdot. l-1) and Cmax (4.5 .+-. 0.1 .mu.mol .cntdot. h-1) than the microsize brands of griseofulvin (AUC.infin.0: 58 .+-. 7, and 45 .+-. 6 .mu.mol .cntdot. h .cntdot. l-1; Cmax: 1.7 .+-. 0.2, and 1.5 .+-. .mu.mol .cntdot. l-1; G and L, resp.), but the same tmax at the third hour. These results correspond with the in vitro liberation data. Contradictory results of the bioavailability are found by determining the amount of 6-demethylgriseofulvin eliminated in urine. The elimination of this main metabolite after dosing with L is lower (0.18 .+-. 0.02 mmol) than those of the other two brands, which do not differ (0.31 .+-. 0.04; 0.32 .+-. 0.02 mmol, G and GP, resp). It is concluded that the determination of bioavailability only by means of the eliminated amount of a metabolite in urine may produce false results.