Plasma Concentration and Urinary Excretion Kinetics of Acetyl Strophanthidin

Abstract

The pharmacokinetics of acetyl strophanthidin (AS) were studied in dogs and human subjects by the use of a newly developed radioimmunoassay. This method has a sensitivity of 0.1 ng of AS per ml and is applicable to direct measurement of AS in unextracted plasma, urine, or bile. After administration of a single intravenous (i.v.) dose of 1.0 mg of AS to 17-25-kg mongrel dogs, the principal exponential decline of plasma AS concentration began 20-60 min after the injection and had a mean half-life (T^½) of 83 ± 19 min (sd). Mean total urinary excretion of AS was 13.3 ± 4.8% of the i.v. dose and occurred with a mean T^½ of 79 ± 10 min. Biliary excretion of AS accounted for only 1.5-2.1% of the i.v. dose. After i.v. administration of 1.0 mg of AS to seven human subjects, the principal exponential decline of plasma AS concentration began 10-30 min after the infusion and had a mean T^½ of 2.3 ± 0.2 hours. Urinary excretion of AS, studied in two patients, accounted for an average of 21.8% of the i.v. dose and occurred with a mean T^½ of 2.4 hours. Thus the plasma level T^½ of AS in human subjects is about tenfold shorter than the 22-hour T^½ previously observed for the relatively short-acting cardiac glycoside ouabain, in agreement with the known brief duration of pharmacologic effects of acetyl strophanthidin.