Steady-state plasma levels of flunarizine in chronically treated patients

Plasma levels were measured at different times during long-term flunarizine treatment (duration 1--45 months, median: 6 months) of 50 patients with intermittent claudication. The dose was gradually reduced, within one month, from an initial dose of 30 mg daily to a maintenance dose of 10 mg daily. Plasma levels, measured by HPLC-method, showed considerable individual differences, ranging between less than 0.02 microgram/ml and 0.25 microgram/ml. Levels between 0.05 and 0.1 microgram/ml were found in 46% of the patients. Individual measurements clearly showed dose-related plasma-levels. There were no signs of accumulation. Side-effects were related to the dose rather than to the levels. There was no correlation between clinical improvement and plasma levels. An extensive first-pass metabolism in the liver is suggested as a possible explanation for the varying inter-individual plasma levels.