Clinical pharmacokinetics of propranolol

Propranolol is completely absorbed after oral administration and widely distributed throughout tissues. Elimination occurs almost wholly by metabolic transformation in the liver and excretion of the resultant products in the urine. An active metabolite, 4-hydroxypropranolol and possibly other active compounds have been identified; the former only after oral administration. After intravenous administration, hepatic extraction is so efficient that drug clearance is dependent on liver blood flow. After oral administration, propranolol kinetics depend on both dose and duration of therapy, but hepatic extraction remains relatively high and leads in presystemic ('first-pass') elimination and low systemic availability. During continued administration, plasma concentrations vary quite widely due to genetic differences superimposed on which are certain constitutional factors, such as age, and environmental factors such as smoking, other drugs, and perhaps diet. Hepatic, renal, thyroid and some gastrointestinal diseases as well as hypertension, malnutrition and hypothermia may be associated with alterations in propranolol disposition, all of which are consistent with the pathophysiology of these diseases.