The in vitro liberation and the bioavailability of different brands of griseofulvin in plasma and urine in man.

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 AUCo infinity (140 +/- 24 mumol . h . l-1) and Cmax (4.5 +/- 0.1 mumol . h-1) than the microsize brands of griseofulvin (AUCo infinity:58 +/- 7, and 45 +/- 6 mumol . h . l-1; Cmax:1.7 +/- 0.2, and 1.5 +/- 0.2 mumol . l-1; G and L, resp.), but the same tmax at the third hour. There 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.

Investigation into the species-specific deacylation of penta-acetyl-gitoxin.

Penta-acetyl-gitoxin (PAG) shows species-specific deacylation to 16-acetyl-gitoxin (16 AG; I and III) or gitoxin (II and IV) by homogenates of liver and intestinal mucosa of man (I), rabbit (II), guinea-pig (III) and rat (IV), whereas it is degraded into tri- and tetra-acetates by homogenates of guinea-pig myocardium as well as by human blood and serum. The identity of the principal and chloroform-extractable metabolities in human urine after PAG administration with 16-AG has been demonstrated by mass spectrometry.

Pharmacokinetic investigations with 3H-penta-acetyl-gitoxin in volunteers and patients with respect to the occurrence of drug latentiation.

After oral administration of 3H-penta-acetyl-gitoxin (Pengitoxin W.H.O., Pentagit) 1.5 mg to four volunteers, serum radioactivity diclines with a half-life of 62 +/- 10 hours. After an oral maintenance dose of 0.4 mg pengitoxin in five digitalized patients, four of them with a cannulated bile duct, serum radioactivity declines with half-life of 56 +/- 8 hours. In volunteers within 4 days 50.7% of the administered radioactivity is excreted in urine; in the patients 52.3% in urine and 28.0% in bile. By thin-layer chromatographic studies, 16-acetyl-gitoxin was charactrized as the main metabolite in serum, bile and urine. Furthermore, in the first 8 hours after administration, two additional metabolites occur in urine.