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Effect of thyrotoxicosis on liver blood flow and propranolol disposition after long‐term dosing
Author(s) -
Wells Peter G,
Feely John,
Wilkinson Grant R,
Wood Alastair J J
Publication year - 1983
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1983.81
Subject(s) - propranolol , euthyroid , medicine , dosing , volume of distribution , drug , pharmacokinetics , blood flow , distribution (mathematics) , oral administration , therapeutic index , endocrinology , pharmacology , thyroid , mathematical analysis , mathematics
The effects of thyrotoxicosis on liver blood flow and propranolol disposition were followed in five patients while thyrotoxic and when euthyroid. Propranolol was taken orally to achieve steady state and then radiolabeled drug was given simultaneously by intravenous injection. Thyrotoxicosis was associated with doubling of both oral and systemic clearances of unbound propranolol, which resulted in an approximately 50% reduction in blood concentrations after oral doses. These changes were attributable to increases in hepatic blood flow and drug‐metabolizing activity of the liver. The propranolol elimination t½ was not affected by thyrotoxicosis since the enhanced clearance was offset by a change in volume of distribution. These findings may explain the reduction of plasma propranolol concentration and many of the therapeutic failures reported in the treatment of thyrotoxicosis. The dose required to achieve therapeutic blood concentrations of propranolol in thyrotoxic patients is variable and will usually be substantially larger than that required for euthyroid patients. Clinical Pharmacology and Therapeutics (1983) 33, 603–608; doi: 10.1038/clpt.1983.81