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Bopindolol

A Review of its Pharmacodynamic and Pharmacokinetic Properties and Therapeutic Efficacy

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An Erratum to this article was published on 01 February 1991

Summary

Synopsis

Bopindolol is a nonselective β-adrenoceptor antagonist with partial agonist activity which is used in the treatment of hypertension. The drug is rapidly metabolised to an active hydrolysed form. The antihypertensive effects of bopindolol 0.5 to 4mg are sustained for more than 24 hours after once daily dosing, and the drug appears similar in efficacy to propranolol, metoprolol, atenolol, pindolol and slow release nifedipine in the treatment of mild to moderate forms of this disease. In limited trials bopindolol has also successfully reduced symptoms in patients with angina pectoris, anxiety and essential tremor. Thus, bopindolol is an effective and well-tolerated β-adrenoceptor antagonist

Pharmacodynamic Properties

Bopindolol is metabolised in vivo to benzoic acid and the nonselective β-adrenoceptor antagonist hydrolysed bopindolol. Bopindolol causes a dose-dependent inhibition of isoprenaline (isoproterenol)-induced tachycardia in animals ( 17 times more potent than propranolol in vitro and 4 times more potent in vivo) In healthy volunteers, exercise-induced tachycardia was reduced markedly (17 to 25%) following 1 and 2mg doses of bopindolol, with only small further reductions occurring with higher doses. Bopindolol was 10 times more potent than pindolol and 100 times more potent than atenolol in this effect. Peak β-adrenoceptor antagonist effects occur about 3 hours after administration, with evidence of continued effects over a relatively long period. Thus, the isoprenaline dose-response curve in patients with hypertension was still shifted significantly to the right 24 hours after a single 2mg oral dose of bopindolol

Bopindolol is a nonselective β-adrenoceptor antagonist, inhibiting exercise- and isoprenaline-induced tachycardia and renin release (β1-mediated effects) and influencing peripheral blood vessels and tremor (β2-mediated effects). The partial agonist activity of bopindolol is demonstrated by reduced exercise-induced tachycardia, but evidence is conflicting as to whether bopindolol has an effect on resting heart rate. Like other agents with partial agonist activity, rebound effects are absent or minimal following withdrawal of bopindolol

In patients with essential hypertension, bopindolol 2mg significantly reduced heart rate, blood pressure and cardiac output. The rise in total peripheral resistance (TPR) accompanying the initial reduction in cardiac output was not evident 24 hours after a single oral dose, although blood pressure was still significantly reduced. Bopindolol has no detrimental effects on left ventricular function. In patients with coronary artery disease, ST segment depression was attenuated and myocardial oxygen consumption was reduced. Renal function is unaffected by bopindolol, although plasma renin activity (PRA) is significantly decreased. Lung function in patients with chronic obstructive lung disease was unaffected by low doses (≤ 2mg daily) of the drug but higher doses of 8mg did increase airways resistance, and this aspect of bopindolol’s profile requires further attention. The effects of bopindolol on the plasma lipid profile are variable and do not appear clearly detrimental, but also deserve additional study

Pharmacokinetic Properties

The pharmacokinetic profile of bopindolol has been studied in healthy subjects. Bopindolol is well absorbed, with peak plasma concentrations occurring about 2 hours after administration, and is rapidly metabolised to the active hydrolysed derivative. Bioavailability is 66 to 70%. The volume of distribution is 148L after intravenous and about 202L after oral administration. Linear pharmacokinetics are apparent over the range of doses from 1 to 4mg. The metabolism of bopindolol is subject to debrisoquirte-type polymorphism, although to a lesser extent than metoprolol. Although early studies found the elimination half-life of bopindolol to be 4 to 5 hours, more sensitive assay methods have determined the half-life to be about 10 hours. Total body clearance varies widely from 16 to 99 L/h

Therapeutic Efficacy

Bopindolol reduces blood pressure significantly from baseline levels in patients with mild to moderate essential hypertension receiving daily doses of 0.5 to 4mg daily for from 4 weeks to 12 months. Initial blood pressure reductions of 6.1 to 15.3% were generally maintained in the long term with no tolerance reported. Heart rates were reduced by 5.2 to 21.6%. Adding chlorthalidone or other diuretics or, in 1 trial, nifedipine, caused further reductions in blood pressure compared with bopindolol monotherapy. Short term (up to 4 weeks) studies with limited numbers of patients demonstrated no significant differences in antihypertensive efficacy between daily dosages of bopindolol 0.5, 1 and 2mg, or between lmg once daily and 8mg once weekly dosage regimens

When compared with daily dosages of atenolol 50 to 200mg, metoprolol 100 to 400mg, pindolol (mean 18.5mg) and propranolol 120 to 480mg in the treatment of small numbers of patients with hypertension, bopindolol 0.5 to 4mg daily resulted in similar reductions in both blood pressure and heart rate. Daily dosages of bopindolol 1 and 2mg were similar in antihypertensive efficacy to slow release nifedipine 20mg twice daily in achieving blood pressure normalisation

Limited clinical experience to date has shown bopindolol ≤ 2mg daily to increase the maximum exercise load and reduce the exercise heart rate in patients with angina, while resting heart rate and ejection fraction tended to be unaffected. In small comparative trials angina severity and sublingual nitroglycerin (glyceryl trinitrate) consumption were significantly reduced by both bopindolol 1 to 4mg daily and metoprolol 100 to 400mg daily for 3 weeks; significantly fewer angina attacks occurred in patients receiving bopindolol 2mg daily than in recipients of atenolol 200mg daily for 12 weeks. Bopindolol 2mg for 3 weeks tended to be more effective than nifedipine 3 times daily although both drugs were superior to placebo

In 1 study of 100 patients those receiving bopindolol appeared to have lower levels of presurgical anxiety and better sleep and coordination than those patients receiving lorazepam or butalbital, and 2 weeks’ treatment with bopindolol improved essential tremor in 10 of 11 patients

Clinical Tolerability

Bopindolol 0.5 to 4mg is well tolerated by most patients. In small studies no significant differences in the incidence and severity of adverse effects have been reported for bopindolol, pindolol, metoprolol, propranolol and atenolol, other than more frequent reports of ‘pressure on the heart’ in bopindolol recipients with hypertension. Bopindolol was better tolerated than nifedipine, particularly with respect to leg oedema and tiredness/dizziness. The most common adverse effects reported during bopindolol therapy for up to 1 year were fatigue, sleeplessness, vivid dreams, depression, dizziness, gastrointestinal upset, palpitations and headache

Dosage and Administration

The effective dosages of bopindolol in all clinical trials in patients with hypertension or angina pectoris appear to be between 0.5 and 4mg daily, with 1 to 2mg being optimal. The addition of a diuretic increases the antihypertensive effects of bopindolol

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Authors and Affiliations

  1. The Queen’s University of Belfast, Belfast, Northern Ireland

    Dean W. G. Harron, Karen L. Goa & Heather D. Langtry

  2. Adis Drug Information Services, Auckland, New Zealand

    Dean W. G. Harron, Karen L. Goa & Heather D. Langtry

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Various sections of the manuscript reviewed by: J.- P. Boissel, Hôpital Neuro-Cardiologique, Unité de Pharmacologie Clinique, Hôpitaux de Lyon, Lyon, France; S.A. Doggrell, Department of Pharmacology and Clinical Pharmacology, School of Medicine, University of Auckland, Auckland, New Zealand; P. Fitscha, Facharzt fur Innere Medizin, Vienna, Austria; R.L. Galeazzi, Department of Medicine, University of Bern, Bern, Switzerland; D.C. Harrison, University of Cincinnati Medical Center, Cincinnati, Ohio, USA; H. Hertzeanu, Cardiac Rehabilitation Institute, Tel Aviv University, The Chaim Sheba Medical Center, Tel-Hashomer, Israel; S. Imai, Department of Pharmacology, Niigata University School of Medicine, Niigata, Japan; T. Ishibashi, Department of Pharmacology Niigata University School of Medicine, Niigata, Japan; N.M. Kaplan, Department ot Internal Medicine University of Texas Health Science Center, Dallas, Texas, USA; C. Mazzola, Istituto di Ricovero e Cura a Carattere Scientifico, Servizio di Cardiologia, Centro per le Malattie Cardiovascolari e l’Ipertensione Arteriosa, Casatenovo, Italy; C.J.C. Roberts, Department of Medicine, Bristol Royal Infirmary, University of Bristol Bristol, England; R.R. Rosenthal, Johns Hopkins Asthma and Allergy Center at the Francis Scott Key Medical Center, Baltimore, Maryland, USA; H. Sato, Osaka University School of Medicine, First Department of Medicine, Osaka, Japan

An erratum to this article is available at http://dx.doi.org/10.1007/BF03260125.

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Harron, D.W.G., Goa, K.L. & Langtry, H.D. Bopindolol. Drugs 41, 130–149 (1991). https://doi.org/10.2165/00003495-199141010-00010

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