Pharmacokinetic investigations in man of two acetyl derivatives of 16alpha-gitoxin.

3H-16-acetyl-16alpha-gitoxin or 3H-penta-acetyl-16alpha-gitoxin were injected iv or administered po to 15 volunteers and 3 patients. The elimination half-life and excretion in urine within 4 days were estimated as a percentage of the administered radioactivity, and metabolic studies on the fate of the administered glycosides were performed. In volunteers the following results were obtained: 3H-16-acetyl-16alpha-gitoxin 1 mg iv.: 50 +/- 11 h, 28.3 +/- 4.1%; 3H-16-acetyl-16alpha-gitoxin 1mg po: 48 +/- 8 h, 25.4 +/- 2.8%; 3H-penta-acetyl-16alpha-gitoxin 2 mg po: 51 +/- 12 h, 20.7 +/- 3.2%, respectively. In 3 patients with a cannulated bile duct 9.9% (mean) of the administered 3H-16-acetyl-16alpha-gitoxin was excreted. By comparison of the radioactivity excreted in urine following the 2 routes of 16-acetate administration, the percentage absorption was calculated to be 88.5%. In serum and urine 16-acetyl-16alpha-gitoxin and 16alpha-gitoxin were found as possible metabolites of both glycosides, in the ratio of 75-85:15-25, and both metabolites were also found in bile. Within 16 h after penta-acetate administration, two additional metabolites (bis-acetyl-derivatives of 16alpha-gitoxin) were detected in serum and urine within 16 h after administration of penta-acetate.