Pharmacology of propranolol in patients with cirrhosis and portal hypertension.

Arthur, M. J. P.; Tanner, A R; Patel, Chintan; Wright, Ralph; Renwick, A. G.; George, Charles F.

doi:10.1136/gut.26.1.14

Cited by 31 publications

(23 citation statements)

References 18 publications

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“…Lebrec et al (1983) compared the pharmacokinetics of 40 mg daily for 1 month in eight cirrhotic patients with 12 normal controls and showed that the maximal plasma concentration and half-life were significantly increased in patients. Arthur et al (1985) examined propranolol levels in 10 cirrhotic patients who were given 160 mg daily of a long acting preparation for 7 days. A steady state was established after 3 days and levels in most patients were must higher than control data obtained from the literature (Leahey et al, 1980).…”

Section: Discussionmentioning

confidence: 99%

A comparative pharmacokinetic study of conventional propranolol and long acting preparation of propranolol in patients with cirrhosis and normal controls.

Watson

Bastain

Larkin

et al. 1987

Brit J Clinical Pharma

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1 Six male patients with alcoholic cirrhosis and seven normal control subjects were each given 80 mg twice daily of conventional propranolol for 1 week and 160 mg once daily of a long acting preparation (LA) of propranolol for 1 week. 2 Plasma propranolol levels were measured at regular intervals on the first and seventh days of both weeks and also following an acute intravenous infusion of 10 mg propranolol on a separate occasion. 3 After the single intravenous dose the elimination half‐life tended to be prolonged in the cirrhotic group (median 7.15 h) compared with controls (median 2.92 h) (P = 0.055). 4 After multiple oral dosing with 80 mg twice daily of conventional propranolol the steady‐state plasma concentration (Css), area under the curve (AUC tau), peak concentration (Cmax) and trough concentration (Cmin) were significantly higher in cirrhotic patients and the peak: trough ratio (Cmax/Cmin) was significantly lower than controls. 5 After multiple oral dosing with 160 mg LA once daily Cmin was significantly higher than Cmax/min significantly lower in cirrhotic patients; Css, AUC and Cmax were higher than controls but not statistically different. 6 Within both subject groups the bioavailability of 80 mg twice daily of conventional propranolol tended to be greater than 160 mg LA once daily. Cmax was significantly higher in both groups and Css higher in the cirrhotic group with conventional propranolol. 7 In the cirrhotic group the mean reduction in supine heart rate in the steady state was 31.8% with conventional 80 mg twice daily propranolol and 23.75% with 160 mg LA once daily.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

A comparative pharmacokinetic study of conventional propranolol and long acting preparation of propranolol in patients with cirrhosis and normal controls.

Watson

Bastain

Larkin

et al. 1987

Brit J Clinical Pharma

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“…We previously reported that nad olol, a noncardioselective beta-blocker like propranolol, lowers portal pressure in pa tients with cirrhosis [2] and that this effect persists after 6 months of treatment [3]. In comparison with propranolol, which was more extensively investigated [4][5][6][7][8] and more frequently employed in the prevention of re bleeding in cirrhosis [9][10][11][12], nadolol has the following characteristics [13]: long serum half-life, low hepatic metabolism, absence of effects on central nervous system since the drug does not cross the blood-brain barrier due to its low lipid solubility. Furthermore, in patients with arterial hypertension, nadolol, unlike propranolol, has been shown to main tain renal blood flow [14.…”

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confidence: 99%

Nadolol for Prevention of Variceal Rebleeding in Cirrhosis: A Controlled Clinical Trial

et al. 1987

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Nadolol, a nonselective beta-blocker, has been shown to decrease portal pressure in patients with cirrhosis at the same degree as propranolol. No data are available, however, about its effect on rebleeding rate and mortality in patients undergoing prevention of rebleeding from esophageal varices. A prospective randomized clinical trial was performed in patients with cirrhosis who survived a documented episode of variceal hemorrhage. 12 patients received nadolol, 12 placebo. Patients with child’s C grade, tense ascites, renal failure, contraindications to beta-blocker, or age > 70 were not included. After a follow-up of up to 145 weeks, 9 patients in the nadolol group and 4 in the placebo group survived free from rebleeding (log-rank test: χ² = 4.35, p < 0.05). Survival was not statistically different in the two groups (1 death in the nadolol group, 3 in the placebo group). In conclusion, nadolol appears to represent an effective therapy in the prevention of variceal rebleeding in cirrhotic patients.

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“…However this result should be interpreted with caution since: a) the number of patients studied was small, b) the Child Pugh score is an approximate reflection of hepatic function (Barbare et al, 1985), c) the most prominent abnormalities of kinetics have been found in patients with serum albumin concentration below 30 g 1-' (Arthur et al, 1985;Branch et al, 1976). Finally a decrease in propranolol clearance was not only dependent on liver activity but also on the volume of blood shunted away from the hepatocytes.…”

Section: Pharmacokineticsmentioning

confidence: 92%

“…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. Unlike the result reported for non cirrhotic subjects (Leahey et al, 1980;Serlin et al 1983), the degree of ,3-adrenoceptor blockade was not significantly different between C and LA propranolol in these cirrhotic patients.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

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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Pharmacology of propranolol in patients with cirrhosis and portal hypertension.

Cited by 31 publications

References 18 publications

A comparative pharmacokinetic study of conventional propranolol and long acting preparation of propranolol in patients with cirrhosis and normal controls.

A comparative pharmacokinetic study of conventional propranolol and long acting preparation of propranolol in patients with cirrhosis and normal controls.

Nadolol for Prevention of Variceal Rebleeding in Cirrhosis: A Controlled Clinical Trial

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

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