Propranolol dosage, plasma concentration, and beta blockade

Mullane, John F.; Kaufman, Joel M.; Dvornik, D.; Coelho, Jaime B.

doi:10.1038/clpt.1982.225

Cited by 39 publications

(12 citation statements)

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“…Dosage was titrated in order to yield plasma levels between 50 to 150 ng per ml. The measurement of plasma concentrations of propranolol has been shown to provide a better estimate of @-blockade than the reduction of resting heart rate (17), and levels above 50 ng per ml are associated with significant p-blockade (18). In our patients, these levels resulted in a significant reduction of resting heart rate and a large increase in the dose of isoproterenol required to increase pulse rate by 25 beats per minute.…”

Section: Resultsmentioning

confidence: 66%

Propranolol for the prevention of recurrent variceal hemorrhage: A controlled trial

et al. 1986

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We conducted a prospective, randomized single-blind trial of propranolol for the prevention of recurrent variceal bleeding. Seventy-nine patients shown to have variceal hemorrhage at endoscopy were included in the study within 72 hr following diagnosis. Fifty-seven patients had alcoholic cirrhosis, 10 cryptogenic cirrhosis, 6 posthepatitic cirrhosis, 4 biliary cirrhosis, 1 portal vein thrombosis without cirrhosis and 1 idiopathic portal hypertension. The severity of liver disease at inclusion was assessed according to the Pugh modification of the Child-Turcotte classification: 9 (11%) had Class A; 41 (52%) Class B, and 29 (37%) Class C disease. Patients were randomly assigned by sealed envelope to the propranolol group (42 patients) or the placebo group (37 patients). Propranolol dosage was titrated in order to produce plasma concentrations of propranolol of 50 to 150 ng per ml. beta-blockade was also confirmed by isoproterenol testing. The cumulative percentages of patients free of rebleeding 1 and 2 years after inclusion were 31 and 21% in the propranolol group, and 25 and 17% in the placebo group; both differences were not significant. Cumulative 1 and 2 years survival were also comparable: 64 and 54% in the propranolol group vs. 70 and 63% in the placebo group. There was no evidence for a therapeutic effect of propranolol after adjusting for potential confounding variables by multiple logistic regression. We conclude that propranolol is not effective for the prevention of variceal rebleeding, when administered early following the initial bleed, in cirrhotics unselected with respect to the severity of the liver disease.

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Section: Resultsmentioning

confidence: 66%

Propranolol for the prevention of recurrent variceal hemorrhage: A controlled trial

et al. 1986

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“…Esler et al (1977) have estimated that the fall in blood pressure in patients with hypertension was significant with concentrations ranging from 3 to 30 ng ml-'. Mullane et al (1982) have observed that with plasma concentrations between 0.5 and 5 ng ml-' 60% of subjects treated with propranolol had significant 3-adrenoceptor blockade. The halflife of the pharmacological effect of conventional propranolol has been estimated to be 20 h measured at rest and 14 h evaluated by exercise test while the chemical elimination half-life is only 3-8 h (Wellstein et al, 1985).…”

Section: Discussionmentioning

confidence: 98%

“…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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“…The value of the exercise peak ,3-adrenoceptor blockade was similar to that observed in non cirrhotic patients, 28 to 40% (Leahey et al, 1980;Serlin et al, 1983;Coltart & Shand, 1970;Hager et al, 1981;Mullane et al, 1982;Pine et al 1975) and in cirrhotic patients, 36% (Mills et al, 1984). Thus, unlike others (Arthur et al, 1985), we consider that the different pharmacokinetics of propranolol in patients with cirrhosis does not result in excessive 3-adrenoceptor blockade.…”

Section: Pharmacodynamicsmentioning

confidence: 60%

Pharmacodynamic and pharmacokinetic study of propranolol in patients with cirrhosis and portal hypertension.

Calès

Grasset

Ravaud

et al. 1989

Brit J Clinical Pharma

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1. The aim of this study was to investigate the pharmacokinetics and the beta‐adrenoceptor blocking activity according to time of conventional (C) and long acting (LA) propranolol in cirrhotic patients. Twenty‐four patients with alcoholic cirrhosis and oesophageal varices were randomly assigned to receive either 160 mg C propranolol, 160 mg LA propranolol or placebo acutely and then following repeated administration (acute and chronic phases). Thereafter propranolol concentrations and beta‐adrenoceptor blockade (resting and exercise heart rates) were measured at different intervals. 2. The Cmax was significantly higher with C propranolol in both phases. The time of Cmax was significantly later with LA propranolol in both phases. The AUCs were significantly higher after chronic administration with both formulations of propranolol. 3. The exercise peaks of beta‐adrenoceptor blockade were similar between the two formulations and between the two phases of administration of propranolol. The duration of effective beta‐ adrenoceptor blockade was significantly longer in the chronic phase and seemed to be longer with LA than with C propranolol although this was not significant (72 +/‐ 31 vs 48 +/‐ 18 h, respectively). 4. There was a significant correlation between the log propranolol concentration and exercise heart rate but not with resting heart rate. No correlation could be demonstrated between pharmacological data and the Child Pugh score. 5. We conclude that in cirrhotic patients exercise testing was a reliable method in the assessment of beta‐adrenoceptor blockade. Pharmacology of propranolol was found to be different according to the formulation or to the phase of administration.

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Propranolol dosage, plasma concentration, and beta blockade

Cited by 39 publications

References 0 publications

Propranolol for the prevention of recurrent variceal hemorrhage: A controlled trial

Propranolol for the prevention of recurrent variceal hemorrhage: A controlled trial

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

Pharmacodynamic and pharmacokinetic study of propranolol in patients with cirrhosis and portal hypertension.

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