Pharmacokinetics of NS-49, a phenethylamine class alpha 1A-adrenoceptor agonist. 2nd communication: Absorption and excretion in rabbits, dogs and monkeys after a single administration of 14C-NS-49.

The absorption and excretion of NS-49 ((R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulfonanilide hydrochloride, CAS 137431-04-0), a phenethylamine class alpha 1A-adrenoceptor agonist, were studied in male rabbits, dogs, and monkeys after intravenous or oral administration of 14C-NS-49. After single oral administration of 14C-NS-49 (1 mg/kg) to rabbits and dogs, the plasma concentrations of radioactivity and NS-49 reached maximums at about 2 h, then decreased triexponentially. In monkeys, both maximums were reached 3 h after administration, and both concentrations decreased biexponentially. Most of the plasma radioactivity was due to unchanged NS-49 in the rabbits and dogs, indicating poor metabolism of this drug. In the monkeys, however, the percentage of unchanged NS-49 in the plasma radioactivity was low, about 20%, during a 24-h period after oral administration. After intravenous and oral administrations of 14C-NS-49, radioactivity was primarily excreted in the urine in all the species tested. The absorption rates found by comparing the urinary excretions of radioactivity after both routes of administration were 71% for rabbits, 92% for dogs, and 95% for monkeys. The percentages of NS-49 in the radioactivity excreted in the urine after intravenous and oral administrations, respectively, were 77% and 68% for rabbits, 96% and 96% for dogs, and 57% and 29% for monkeys. The systemic availability calculated from the unchanged drug excreted in the urine was similar to the absorption rates for rabbits and dogs. This indicates that first-pass metabolism of this drug is very limited in both species. The systemic availability for monkeys, however, was about half the absorption rate due to the first-pass effect. Renal clearance accounted for most of the total clearance for rabbits and dogs, but only about half that for monkeys.