Clinical Pharmacology of Propranolol in Infants and Children

Gian Maria Pacifici

doi:10.31579/2768-0487/037

Abstract

Propranolol is α nonselective β adrenergic receptor antagonist with equal affinity for β1 and β2 adrenergic receptors, lacks intrinsic sympathomimetic activity, and does not block α receptors. Propranolol is absorbed following oral administration and consists in two enantiomers, the (-) enantiomer is the active form and is cleared from the body more slowly than the inactive (+) enantiomer. Much of propranolol is metabolized in the liver and the metabolites of propranolol are 4-hydroxypropranolol, 5-hydroxypropanolol, N-desisopropranol, and propranolol β-D-glucuronide. The oral dose of propranolol hydrochloride is 250 to 750 µg/kg thrice-daily in infants and in children it is 200 to 500 µg/kg thrice-daily or 4 times-daily. Propranolol has been found efficacy and safe in infants and children but may induce adverse-effects. The elimination half-life of propranolol is about 15 hours in term and preterm infants and the distribution volume of propranolol is larger than the water volume. Propranolol interacts with drugs. Halofenate, phenytoin, phenobarbitone, rifampicin, and ethanol which affect the clearance of propranolol, and chlorpromazine and cimetidine inhibit the metabolism of propranolol. The prophylaxis, treatment, and trials with propranolol have been extensively studied in infants and children. Propranolol crosses the human placenta but it does not equilibrate between the maternal and foetal compartment and migrates into the beast-milk. The aim of this study is to review the published of propranolol dosing, efficacy and safety, effects, adverse-effects, metabolism, pharmacokinetics, interaction with drugs, prophylaxis, treatment and trials in infants and children and propranolol transfer across the human placenta and migration into the beast-milk.

Highlights

The β adrenergic receptor antagonists are classified as non-subtypeselective (“first generation”) β1 selective (“second generation”), and nonsubtype- or subtype-selective with additional cardiovascular action (“third generation”)
Halofenate, phenytoin, phenobarbitone, rifampicin and ethanol affect the clearance of propranolol and chlorpromazine and cimetidine inhibit the metabolism of propranolol [32]
Propranolol treatment is safety and efficacy in infantile haemangioma and a higher response-rate can be gained with early treatment and a prolonged course of therapy [47]

Summary

Introduction

The β adrenergic receptor antagonists are classified as non-subtypeselective (“first generation”) β1 selective (“second generation”), and nonsubtype- or subtype-selective with additional cardiovascular action (“third generation”). These last drugs have additional cardiovascular properties (especially vasodilation) that seem unrelated to β blockage. There is great interindividual variation in the presystemic clearance of propranolol by the liver; this contributes to enormous variability in plasma concentrations (about 20fold) after oral administration of the drug and to the wide dosage range for clinical efficacy. The clearance of propranolol may vary with the hepatic blood flow and liver disease and may change during the administration of other drugs that affect the hepatic metabolism. For the treatment of hypertension and angina, the Auctores Publishing – Volume 3(3)-037 www.auctoresonline.org

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