Pharmacokinetics and metabolism of a new beta-adrenergic blocking agent, the 1, ter-butyl-amino-3-(1,2,3,4-tetrahydro-1,4-ethano-8-hydroxy-5-naphthoxy)-2-propanol (K 5407)

A beta-blocking agent, the 1,ter-butylamine3-(1,2,3,4-tetrahydro-1,4-ethano-8-hydroxy-5-naphthoxy)-2-propanol (K5407) was synthesized with 14C and 3H and its pharmacokinetics in the dog and man were investigated after i.v. and oral administration. K5407 was rapidly absorbed after oral dosing and plasma peaks were within 1 hour. Concentrations of unchanged compound were found to be very small. After i.v. injection the levels decreased with a half-life of 2-3 hours. Excretion was mainly in the urine and amounted to about 72% of the dose in the dog and about 85% in man for both administration routes. Tissue radioactivity distribution studies in male and in pregnant mice after i.v. injection showed rapid body diffusion, passage through the blood-placenta barrier and no localization in the central nervous system. The metabolic process in dog and human urine was studied. Little unchanged compound was found (5% in the dog and 13% in man after i.v. injection and about 1% in both species after oral dosing). Conjugation processes represented the main route of biotransformation. Five metabolites, resulting from side chain degradation of the compound, were identified in dog urine and in trace quantities in human urine.