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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.

The pharmacokinetics after oral administration of the beta-blocker metipranolol (Disorat) were investigated in 20 patients with liver cirrhosis, 8 of them with portocaval shunt. Twenty healthy persons were used as controls. Kinetic data in patients were not notably different from the normal group, in particular there was no significant difference in the mean serum concentration over 24 hours. In patients with advanced disease the only noteworthy difference was an increase of the linear rate of increase of serum concentrations. Maximal serum concentrations were found with a median of only 0,37 and 0,59 hours after intake, and in controls 0,76 hours after intake. It appears that metipranolol has no hepatic first-pass-effect and that its total clearance remains largely uninfluenced even in severe liver damage. A reduction of dosage in these diseases is thus not required from the pharmacological point of view.

The absorption and distribution of the slightly water-soluble, carbon-14-labelled 1-(2,5-dichlorophenoxy)-3-tert-butylaminopropen-2-ol hydrochloride (1) from sprays and suspension aerosols have been studied in mice. It was found that the blood level and the organ concentrations achieved with suspension aerosols were higher than those obtained with sprays.

The presynaptic adrenergic mechanisms of action of 1-(4-hydroxyphenyl)-2-methylamino-propanol-(1) (4-HMP, oxilofrine) were investigated in the rat. The sympathicomimetic agent is stored in the heart by a mechanism with saturation characteristics, resembling noradrenaline in this respect. Inhibitors of the neuronal and extraneural binding of noradrenaline at the same time suppress the tissular uptake of 4-HMP. Investigations in vivo in the tissular distribution and on the subcellular distribution in the iris, vas deferens and spleen confirm the affinity of 4-HMP for the storage vesicles containing noradrenaline. Stimulation of the spinal nerves results in a release of the sympathicomimetic agent. This underlines the significance of the presynaptic mechanisms of action for the pharmacological properties of 4-HMP.

Pharmacokinetic parameters were determined after the oral administration of a single tablet containing 200 mg celiprolol HCl to 8 healthy volunteers with normal kidney function and 6 patients with stable impaired renal function of different degrees of severity. The plasma levels and the urinary excretion of celiprolol were followed up for 48 hours after administration with the help of specific chemo-analytical methods. The substance was equally well absorbed both by healthy volunteers and patients with renal disease. While the cumulative renal excretion (0 to 48 hours after administration) was reduced from 18.2% in healthy volunteers to 2.3% of the applied dose in kidney patients, the global elimination constant k fell from 0.104 h-1 in healthy volunteers to 0.072 h-1 in the patients with renal disease. It can be assumed that in patients with impaired renal function at least a part of the lacking renal elimination of celiprolol can be taken over by "extrarenal elimination". According to the method of Dettli a reduction in dosage of the beta 1-blocker, celiprolol is not necessary in patients with more or less impaired kidney function.