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Roles of hepatic blood flow and enzyme activity in the kinetics of propranolol and sotalol.
Author(s) -
Pirttiaho HI,
Sotaniemi EA,
Pelkonen RO,
Pitkanen U,
Anttila M,
Sundqvist H
Publication year - 1980
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1980.tb01068.x
Subject(s) - sotalol , propranolol , blood flow , endocrinology , medicine , chemistry , pharmacokinetics , pharmacology , in vivo , enzyme , drug metabolism , metabolism , biochemistry , biology , atrial fibrillation , microbiology and biotechnology
1 The roles of the hepatic blood flow and the drug oxidizing enzyme system in eliminating oral propranolol and sotalol were studied in twelve subjects with biopsy proven liver parenchymal disease. 2 The apparent plasma clearance of propranolol was closely related both to the in vivo (antipyrine test) and in vitro (cytochrome P‐450) indices of the activity of the hepatic mixed function oxidase system. 3 Propranolol clearance had also a clear relationship to the estimated liver blood flow. Altered flow was, however, suggested to be a minor factor when compared with changes in the enzyme system. 4 The elimination rate of sotalol had no correlation to the indices of hepatic drug metabolism or to the estimated liver blood flow. 5 It is concluded that both the deteriorated sinusoidal perfusion and the decreased mass of drug metabolizing enzymes may be responsible for the impaired elimination of oral propranolol in subjects with parenchymal liver disease.