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

  • P. C
  • D. G
  • A. R
 et al. 
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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 oesoghageal 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. The C(max) was significantly higher with C propranolol in both phases. The time of C(max) was significantly later with LA propranolol in both phases. The AUCs were significantly higher after chronic administration with both formulations of propranolol. The exercise peaks of beta-adrenergic 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). 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. 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.

Author-supplied keywords

  • *heart rate
  • *liver cirrhosis
  • *pharmacokinetics
  • *portal hypertension
  • *propranolol/pd [Pharmacology]
  • *propranolol/pk [Pharmacokinetics]
  • *sustained release preparation
  • Adrenergic beta-Antagonists
  • Alcoholic
  • Delayed-Action Preparations
  • Exercise
  • Heart Rate
  • Human
  • Hypertension
  • Liver Cirrhosis
  • Portal
  • Propranolol
  • Time Factors
  • adult
  • aged
  • clinical article
  • exercise test
  • female
  • heart rate
  • human
  • liver cirrhosis
  • male
  • oral drug administration
  • pharmacokinetics
  • portal hypertension
  • priority journal
  • propranolol
  • sustained release preparation

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  • Cales P.

  • Grasset D.

  • Ravaud A.

  • Meskens C.

  • Blanc M.

  • Vinel J.P.

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