Disposition and Metabolism of Atenolol in Animals

1. The disposition of [14C]atenolol (1-[4-carbamoylmethyl[U-14C]phenoxy]- 3-isopropylaminopropan-2-ol, Tenormin‡) has been studied in five species. 2. In the dog, absorption of oral doses of atenolol was virtually complete, and elimination occurred largely via the kidney. In all other species absorption even from aq. soln. was incomplete. 3. Biliary excretion in the rat and dog was minimal. 4. In all species, the major 14C component of 0-24 h urine was atenolol. The pattern of metabolites was similar, showing quantitative rather than qualitative differences. 5. The one significant minor metabolite detected in microsomal preparations and in urine arises by hydroxylation at the methylene carbon of the carbamoylmethyl group. This metabolite has only one tenth of the activity of the parent compound as a β-adrenergic blocking agent in the rat. 6. The pharmacological activity of the drug appears to be due to the parent compound alone.