The Fate of Atropine in the Puppy

Abstract

Abstract: The fate of atropine in newborn, 3 and 6 weeks‐old, 3 months‐old and adult dogs has been investigated with the tritium‐labelled drug. After subcutaneous injection (0.5 mg/kg) maximal plasma concentrations of radioactivity were obtained after 0.5 hr in the two oldest groups and after 1‐1.5 hrs in the three youngest groups. The plasma half‐life of radioactivity was considerably longer in the newborn animals than in the other groups (11.5 hrs as against 3.5‐5.5 hrs). In the three youngest age groups, the urinary excretion of radioactivity was about half that in the adult animals, who excreted about 40 per cent of the injected radioactivity in 4 hrs. Between 50‐90 per cent of the radioactivity in the urine was recovered as the unchanged drug in all age groups in the 2 to 4 hrs interval. There were no consistent differences in the pattern of metabolites in the urine between the different age groups. The concentration of radioactivity in the liver, kidney, submandibular gland, heart, skeletal muscle and brain was investigated at 0.5, 1, 2, 4 and 8 hrs after injection (0.5, 2 and 8 hrs for adult animals). In general, there were no significant differences in organ distribution between the age groups. The radioactivity in the brain consisted exclusively of the unchanged drug. The rate of penetration into the brain and the maximal brain concentrations of the drug showed no significant changes with age. Within the hemispheres, a fall in the concentration of atropine from the cerebral cortex to the lateral ventricles was found in all age groups. The binding of atropine to plasma proteins was about 18 per cent over a wide range of concentrations. No difference in plasma binding in vivo was found between the different age groups.