A pharmacodynamic and pharmacokinetic comparison of pindolol 20 mg retard and a conventional tablet

Abstract

In 10 healthy volunteers the time course of cardiac beta-adrenoceptor blocking activity, plasma levels and cumulative urinary excretion of pindolol were compared during a 4-day course of pindolol 5 mg (Visken) t. d. s., and one tablet of pindolol 20 mg retard (Visken retard) once a day. After oral administration of the 20 mg retard tablet, plasma concentrations of pindolol higher than half the maximum value (1/2 Cp (tmax)) were maintained about 2.5 times as long as after administration of the conventional 5 mg tablet. This is evidence for an important and marked retardation of drug release. During treatment with pindolol 20 mg retard once daily, cardiac beta-adrenoceptor blockade, measured by the reduction in exercise-induced tachycardia and in the exercise-induced rise in systolic blood pressure, at almost all times throughout the 24 h period was at least as great as during treatment with pindolol 5 mg t. d. s. This suggests that patients successfully treated with pindolol 5 mg t. d. s. can be maintained with the same beta-adrenoceptor blockade by a single tablet of pindolol 20 mg retard once daily.

The role of 5-HT1a and 5-HT2a receptors in attention and motor control: a mechanistic study in healthy volunteers

“…Treatments consisted of escitalopram 20 mg + placebo; escitalopram 20 mg + ketanserin 50 mg; escitalopram 20 mg + pindolol 10 mg; and placebo + placebo administered at four different test days separated by a washout period of at least 7 days. Escitalopram, ketanserin and pindolol oral dosages have a C max of 4, 2 and 1 h and a half-life of 27-32, 3-4 and 13-18 h, respectively (Aronson and Delgado 2004;Aellig et al 1981;Hedner et al 1983). An oral dose of 10 mg of pindolol was needed in healthy volunteers to achieve a 37% occupancy of the 5-HT 1a autoreceptor (Rabiner et al 2001).…”

Effect of Lipophilicity on in Vivo Iontophoretic Delivery. II. .BETA.-Blockers.

“…16,18,20,42,43) PD and PP are the most potent in b-blockers used in our study and their minimum effective concentrations are in the range of 10-20 ng/ml (human). 18,19,42,43) Systemic plasma concentrations of PD and PP after 90-min iontophoresis were 10Ϯ3 and 5Ϯ1 ng/ml, respectively (Figs. 2B, F).…”

“…14) Because of their short elimination half-life (from several to less than 6 h), 15) sustained release formulations for oral administration have been developed to prolong the therapeutic effects. [16][17][18][19][20][21] However, the oral absorption of b-blockers is influenced by hepatic first-pass metabolism. 15,22) Thus, the development of transdermal delivery systems may be expected to achieve good maintenance of optimal blood levels and the avoidance of first-pass effects.…”

Comparison of the effect of pindolol and propranolol on heart rate after acute and chronic administration.

“…In one acute study, a rise in supine heart rate was observed (Aellig, 1976). From other studies there has been no evidence for a cumulative effect nor loss of partial agonist activity with chronic dosing (Aellig et al, 1981), nor did cumulative doses of pindolol induce an increase in supine heart rate (Carruthers & Twum-Barima, 1981). The majority of these studies involved the acute administration of pindolol by oral and intravenous routes but as ,3-adrenoceptor blocking drugs are given chronically, it seemed important to compare the effects of a ,8-adrenoceptor blocking drug without partial agonist activity on acute and chronic dosing with a drug with partial agonist activity to see if during chronic administration the 1adrenoceptor blocking effect of the drug would antagonise its own partial agonist activity and as a result have the same effect as a drug without partial agonist activity.…”