Plasma concentrations of propranolol and 4-hydroxy-propranolol at steady-state in neurological patients: intersubject and intrasubject correlations with dose.
Plasma concentrations of propranolol (PROP) and its active 4-hydroxymetabolite were determined in neurological patients receiving chronic therapy with relatively low PROP doses (40-240 mg/day). Plasma PROP concentrations determined before the morning dose were much lower than, but significantly correlated (r = 0.91) with the drug level two hours after dosing. 4-hydroxypropranolol (4-OH-P) was often undetectable (less than 1 ng/ml) in the early morning samples. Plasma concentrations of both parent drug and metabolite determined two hours after the morning dose correlated weakly with the prescribed daily dose. The intrapatient dose-concentration relationship, on the other hand, was strong, particularly for the parent drug. The ratio between 4-OH-P and PROP in plasma was inversely related to the PROP concentration, at least over the lower PROP concentration range (0-100 ng/ml). The usefulness of determining the concentration of the metabolite in the evaluation of the pharmacological action of low doses of PROP is discussed.
D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007206:Individuality; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000097:blood; D011433:Propranolol / Q000031:analogs & derivatives* / Q000097:blood*; D014202:Tremor / Q000097:blood
C001422:4-hydroxypropranolol; D011433:Propranolol