Gunter Bodem

Pharmacokinetic studies of practolol, a beta adrenergic antagonist, in man.

The disposition of practolol after oral and intravenous administration was studied in hypertensive patients. The plasma half‐life was 13.2 hours. After intravenous administration practolol was recovered quantitively in the urine. Its volume of distribution was larger than that of body water, 1.6 L. per kilogram, and its clearance from this volume, 135 ml. per minute, was equal to renal clearance of the drug; both were slightly higher than the creatinine clearance. Despite its weakly basic character, this aromatic alkylamine was not affected by changes in urinary pH from 5.4 to 8.0. These studies indicate that practolol is slowly removed from the body and that it is excreted entirely by the kidneys.

The effect of pindolol on exercise-induced cardiac acceleration in relation to plasma levels in man.

The correlation between the beta receptor blocking activity of pindolol and plasma level was studied in 8 subjects after a 10‐mg oral dose. Exercise tachycardia was markedly reduced over a period of at least 6 hr. Significant effects were recorded 30 min after the drug. For each individual there was a close correlation between log plasma level and beta blockade. The regression lines were parallel as shown by analysis of covariance; the intercepts, however, were significantly different. It can be concluded that there is a correlation between plasma level and beta adrenergic blockade by pindolol, but the data failed to establish in different individuals the blood levels necessary to achieve effective adrenergic blockade.

Pharmacodynamic Studies of Beta Adrenergic Antagonism Induced in Man by Propranolol and Practolol

The pharmacodynamic activities of two beta adrenergic antagonists, propranolol and practolol, were compared in eight hypertensive patients. The activity of each antagonist was established in relation to its blood concentration at maximal and submaximal adrenergic blockade defined by inhibition of exercise tachycardia. Maximal inhibition of exercise tachycardia was comparable with both drugs and averaged 74+/-7% of the control value during drug treatment. This inhibition was achieved with a blood concentration of 2.5+/-0.4 mug/ml practolol and 0.10+/-0.08 mug/ml propranolol. The antagonist activities of these drugs against adrenergic stimulation with isoproterenol infusion indicated a much greater relative potency of propranolol against this stimulus, and in vivo estimates of PA(2) values differed by more than 600-fold. Relative antagonist activity of practolol during isoproterenol stimulation was equivalent both at cardiac (inotropic and chronotropic) and at vascular adrenergic receptors, whereas greater antagonist activity of propranolol was observed at vascular receptors than at cardiac receptors. Thus, the activity of practolol was not limited to cardiac receptors as previously suggested. Practolol did not reduce cardiac output at any dose level and the effect on resting blood pressure was small. Both practolol and propranolol had much greater hypotensive activity during exercise. These studies have defined the differing pharmacodynamic activities on the cardiovascular system of two effective beta adrenergic receptor antagonists and have established the blood levels of these antagonists necessary to achieve effective adrenergic blockade.

Methoden zur Bestimmung von Digoxin und Digitoxin im Blut und ihre klinische Bedeutung

SummarySix methods are described for determining the concentrations of digoxin and digitoxin in blood, as well as the importance of such pharmacokinetic parameters as volume of distribution, blood decay curves, and the relationships between myocardial and plasma concentration discussed for proper interpretation of the plasma concentrations of these cardiac glycosides.ZusammenfassungSechs Verfahren zur Bestimmung von Digoxin- und Digitoxinblutspiegel werden beschrieben und ihre Eignung als Routinemethoden diskutiert. Der zeitliche Ablauf von Blutspiegelkurven, der Verteilungsraum und das Konzentrationsverhältnis zwischen Plasma und Myokard werden als notwendige pharmakokinetische Grundlagen zur Interpretation der Blutspiegel von Herzglykosiden angeführt und die wesentlichen klinischen Anwendungsbereiche besprochen.

Digitaliswirkung auf die Extremitätendurchblutung des Menschen

SummaryThe effect of lanatosid C on the peripheral vascular system was studied in a randomized doubleblind cross-over study. 1 mg lanatosid C in saline or a corresponding volume of saline were applied intravenously for 30 min to 6 healthy subjects. A significant drop of 28% in blood flow and an increase of peripheral vascular resistence at rest of 44% during and after the application of the cardiac glycoside could be seen while the placebo effect was minimal.ZusammenfassungAnhand eines gekreuzten Doppelblindversuchs wurde die Gefäßwirkung von 1 mg Lanatosid C geprüft, welches 6 gesunden Probanden in 30 min intravenös appliziert wurde. Während unter der Infusion von physiologischer Kochsalzlösung keine signifikanten Änderungen der haemodynamischen Parameter eintrat, war bei Digitalisgabe eine Abnahme des Ruhestromvolumens der unteren Extremität und eine Erhöhung des peripheren Gefäßwiderstandes zu beobachten, welche als Gefäßwirkung der Substanz erklärt wird.