ABSTRACT
16-Acetyl-gitoxin, the cardioactive metabolite of pengitoxin, was estimated by the 86Rb uptake technique. In 70 consecutive patients taking an oral maintenance dose of pengitoxin 0.4 mg (Pentagit), the mean plasma concentration was 20.8 +/- 6.7 ng/ml. Toxic signs were not observed up to plasma levels of 40 ng per ml.
Subject(s)
Acetyldigitoxins/analogs & derivatives , Digitoxin/analogs & derivatives , Acetyldigitoxins/blood , Humans , Methods , RadioimmunoassayABSTRACT
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.
