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Direct measurement of propranolol bioavailability during accumulation to steady‐state.
Author(s) -
Wood AJ,
Carr K,
Vestal RE,
Belcher S,
Wilkinson GR,
Shand DG
Publication year - 1978
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.1365-2125.1978.tb00862.x
Subject(s) - propranolol , bioavailability , pharmacokinetics , oral administration , steady state (chemistry) , pharmacology , chemistry , drug , first pass effect , medicine , endocrinology
1. A high performance liquid chromatographic method for the determination of propranolol in human plasma and blood has been developed and used to confirm that cumulation occurred during chronic oral administration, steady‐state being achieved within 48 h of beginning 80 mg of the drug every 8 h. 2. The method was adapted to measure [H3]‐propranolol and native drug in the same blood sample and was applied to determine simultaneously the disposition of i.v. ([H3]‐ propranolol) and orally (non‐labelled) administered drug after single oral dose of 80 mg and when steady‐state had been established on an 80 mg, 8‐hourly regimen. 3. Using this approach it was possible to show that a reduced oral clearance at steady‐state was associated with a smaller reduction in systemic (i.v.) clearance and no change in liver blood flow. A direct estimate of bioavailability was also possible and was found to be increased at steady‐state compared with a single oral dose. 4. We conclude that the accumulation of propranolol during the attainment of steady‐state is due to a reduction in intrinsic clearance, resulting in reduced presystemic hepatic extraction.