[Animal experimental studies on the pharmacokinetics of carteolol]

From investigations in rats and dogs it is known that the proportion of 5-(3-tert-butylamino-2-hydroxy-propoxy)-3, 4-dihydro-2(1H)-quinolinone hydrochloride (carteolol hydrochloride, Endak, Endak mite) absorbed after oral administration is 60-80%. In dogs (as in human beings) most of it is excreted via the kidneys, but in rats biliary elimination predominates. In addition to 8-hydroxycarteolol--which also possesses pharmacological activity--the main metabolites found in dogs and rats are glucuronides of carteolol and 8-hydroxycarteolol. The elimination half-lives in dogs, rats and rabbits are between 1.2 and 3.0 h. Distribution studies point to the existence of a blood-brain barrier (rats and dogs) and a placental barrier (mice). The apparent volume of distribution measured after i.v. injection was from 2.5 to 8.5 l/kg depending on species. Passage into the milk was demonstrated in rats. Plasma protein binding is minimal. In a long-term study in dogs there was no evidence of cumulation except at the very high dosage of 200 mg/kg.