Relationship of propranolol pharmacokinetics to antihypertensive effect and beta-adrenergic blockade in the treatment of hypertension

Krediet, R. T.; Dunning, Arend J.; Offerhaus, L

doi:10.1007/bf00636790

Cited by 10 publications

(4 citation statements)

References 12 publications

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“…Many studies have demonstrated correlations between plasma (or blood) levels of propranolol and its pharmacological effect (Coltart & Shand, 1970;Pine et al, 1975;McAinsh et al, 1978;Mullane et al, 1982) but others could not establish this correlation (Krediet et al, 1980;Lehtonen et al, 1977).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic comparison of two doses of long acting propranolol (80 and 160 mg) in healthy subjects.

Flouvat

Berlin

Cournot

et al. 1989

Brit J Clinical Pharma

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1. The kinetics and dynamics of long acting propranolol 80 mg and 160 mg were examined after single oral doses to 12 healthy volunteers. 2. Long acting propranolol 160 mg produced a twofold increase in mean peak blood propranolol concentration and AUC compared with the lower dose. There was no difference in elimination half‐life, bioavailability and mean residence time of propranolol between the two doses. 3. Resting pulse rate was decreased by long acting propranolol 160 mg but not by the lower dose. 4. Both preparations blocked exercise induced tachycardia during the entire observation period of 29 h. Percentage inhibition of exercise tachycardia was significant at all time points but long acting propranolol 160 mg exhibited a greater reduction at 24 h and 29 h. 5. Increase in systolic blood pressure during exercise was inhibited by both preparations during the entire observation period with no differences between them. 6. The doubling of the dose administered was reflected in blood concentrations but not in pharmacodynamic parameters. Few pharmacodynamic differences were found between the two doses.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic comparison of two doses of long acting propranolol (80 and 160 mg) in healthy subjects.

Flouvat

Berlin

Cournot

et al. 1989

Brit J Clinical Pharma

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“…These investigators concluded that this was because the urinary propranolol concentrations might better reflect total exposure to propranolol over the day than plasma propranolol concentrations. As other authors have failed to find any relationship between the area under the plasma concentration-time curve or mean plasma propranolol concentrations over the day, this seems a somewhat simplistic explanation (Krediet et al 1980). In addition, although failing to find a relationship between plasma propranolol concentrations and antihypertensive effect, a good relationship was found between the extent of Pblockade and the antihypertensive effects of propranolol (Krediet, et al 1980) and it was considered that the antihypertensive effect parallels Pblockade.…”

Section: Does Long Acting Propranolol Maintain Blood Pressure Controlmentioning

confidence: 96%

“…As other authors have failed to find any relationship between the area under the plasma concentration-time curve or mean plasma propranolol concentrations over the day, this seems a somewhat simplistic explanation (Krediet et al 1980). In addition, although failing to find a relationship between plasma propranolol concentrations and antihypertensive effect, a good relationship was found between the extent of Pblockade and the antihypertensive effects of propranolol (Krediet, et al 1980) and it was considered that the antihypertensive effect parallels Pblockade. 60 Thus, in the absence of a clear concentrationeffect relationship it was reasonable to attempt once-daily conventional propranolol therapy for the treatment of hypertension.…”

Section: Does Long Acting Propranolol Maintain Blood Pressure Controlmentioning

confidence: 96%

Pharmacokinetics of Long Acting Propranolol

Nace

Wood

1987

Clinical Pharmacokinetics

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Beta-adrenoceptor antagonists are among the most commonly prescribed classes of drugs. They are indicated for the treatment of diseases such as hypertension and angina pectoris, in which long term therapy is often required. Since many beta-adrenoceptor antagonists have short plasma elimination half-lives, divided daily dosing has often been necessary in order to provide continuous beta-blockade throughout the day. However, such multiple-dose schedules may promote patient non-compliance and failure of the prescribed regimen. Long acting propranolol is a sustained release formulation of propranolol which has been developed to maintain therapeutic plasma propranolol concentrations throughout a 24-hour period while allowing once-daily dosing. Compared with conventionally formulated propranolol, long acting propranolol has a prolonged terminal half-life (8 to 11 hours), due to slower absorption from the gut. Systemic bioavailability of long acting propranolol is 30 to 50% less than that of the conventional formulation. This difference may result from increased hepatic metabolism. Peak drug concentrations are significantly lower than following identical doses of conventional propranolol, and the time to peak drug concentrations following administration is delayed. Relatively constant plasma concentrations and clinically significant inhibition of exercise-induced tachycardia are maintained throughout a 24-hour dosing interval following once-daily long acting propranolol. Once-daily long acting propranolol is as effective as divided doses of conventional propranolol for the treatment of hypertension and angina pectoris. Efficacy also appears comparable with once-daily administration of long acting conventional beta-adrenoceptor antagonists such as atenolol and nadolol. Once-daily long acting propranolol provides clinically significant sustained beta-adrenoceptor blockade and offers the potential for improved patient compliance due to once-daily dosing. Since provision of sustained beta-adrenoceptor blockade appears to be particularly important in the treatment of angina, this may be the principal indication for which long acting propranolol has a therapeutic advantage independent of its potential to improve compliance.

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“…This seems to be consistent with previous studies where even if a significant correlation between plasma levels of several f3-adrenoceptor blockers and fall in some of blood pressures was found, it was of a weak order or equivocal (Anavekar et al, 1975;Collste et al, 1976). Others did not find any correlation between antihypertensive response and plasma concentration of propranolol (Kredit et al, 1980;Lehtonen et al, 1977) or metoprolol (Bengtsson et al, 1975;von Bahr et al, 1976).…”

Section: Discussionmentioning

confidence: 97%

A dose ranging study of atenolol in hypertension: fall in blood pressure and plasma renin activity, beta‐blockade and steady‐state pharmacokinetics.

Ishizaki¹,

Oyama²,

Suganuma³

et al. 1983

Brit J Clinical Pharma

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I The relationship between the oral dosage and plasma concentration of the long-acting cardioselective /3-adrenoceptor blocker atenolol and the antihypertensive response to the degree of f8-adrenoceptor blockade and change in plasma renin activity (PRA) was evaluated in patients with mild-tomoderate essential hypertension in a double-blind, randomized, between-patient, dose-ranging (25, 50 or 100 mg once daily for 4 weeks) study. 2 The optimum, or minimum, daily dose of atenolol to treat patients with mild-to-moderate hypertension was not clearly identified in this study. A between-treatment comparison did not demonstrate that all blood pressure falls were always less in the 25 mg group than in the other two groups. Calculation of ,8-error or the power for the negative results between doses suggested that a large sample size is required to draw a conclusion that no dose-antihypertensive relationship of atenolol exists in the treatment of mild-to-moderate hypertension. 3 A relatively flat plasma concentration-antihypertensive response relationship was observed. 4 Steady-state plasma concentrations of atenolol were dose-related and renal drug clearance was well correlated with individual creatinine clearance.5 ,3-adrenoceptor blockade was better correlated with plasma atenolol concentration. Correlations which were less strong were between plasma drug concentration and change in various blood pressures and between blood pressure falls and /3-adrenoceptor blockade. 6 There was no relationship between the fall in blood pressure and change in PRA. Atenolol appeared to suppress PRA in an all-or-none fashion.

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Relationship of propranolol pharmacokinetics to antihypertensive effect and beta-adrenergic blockade in the treatment of hypertension

Cited by 10 publications

References 12 publications

Pharmacokinetic and pharmacodynamic comparison of two doses of long acting propranolol (80 and 160 mg) in healthy subjects.

Pharmacokinetic and pharmacodynamic comparison of two doses of long acting propranolol (80 and 160 mg) in healthy subjects.

Pharmacokinetics of Long Acting Propranolol

A dose ranging study of atenolol in hypertension: fall in blood pressure and plasma renin activity, beta‐blockade and steady‐state pharmacokinetics.

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