Studies on the pharmacokinetics and the metabolism of gitoxin in the guinea-pig: I. Disposition kinetics following an i.v. bolus of 3H-gitoxin.

Kinetics and metabolism of 3H-gitoxin were determined in the guinea-pig after the i.v. administration of 80 microgram gitoxin/kg. The time course of plasma concentration and urinary amounts remaining to be excreted were described according to the three-compartment linear body model. Apparent half-lives of 4.98 +/- 0.16 hr (plasma) and 24.0 +/- 0.5 hr (urine) were found according to the CH2Cl2-soluble radioactivity. The apparent volume of central compartment and the apparent volume of distribution were estimated with 0.44 +/- 0.05 l/kg and 14.33 +/- 1.131/kg respectively. During 96 hr, approximatively 5.3% of the radioactivity given were eliminated via the kidneys whereas almost 78.7% were recovered in faeces. In animals with bile-duct cannulated, approximatively 82.6% of the dose given were excreted in bile during 6 hr. The hepatic degradation of gitoxin was so fast that almost 70% of the radioactivity recovered in plasma, urine and bile samples after 2 hr could no longer be extracted by dichloromethane. In the lipophilic extracts diginatin and its derivatives were found as possible metabolites of gitoxin. At least four polar metabolites hardly hydrolysable by beta-glucuronidase and by arylsulfatase were detected by TLC in the aqueous extracts from the gastro-intestinal excretions.