Amantadine kinetics in healthy young subjects after long-term dosing

We investigated the disposition of amantadine in 13 healthy, young adults after long-term dosage. Doses of 25, 100, or 150 mg, randomly allocated, were taken at 12-hr intervals in syrup for 31 doses. A 1-compartment open model and complete bioavailability were assumed. Absorption rate was variable with peak concentrations in plasma occurring at 1 to 12 hr. Since the calculated area under the plasma concentration against time curve was proprotional to it, relative bioavailability was independent of dose at steady state. As the dose increased, the apparent volume of distribution decreased. Intra- and intersubject variations in trough plasma drug concentrations at steady state were less than triple for equivalent doses. Elimination of drug from plasma was consistent with a first-order process. Plasma half-lifes (t1/2s) ranged from 10.2 to 31.4 hr and were independent of dose or creatinine clearance. The ratio of renal drug clearance to creatinine clearance ranged from 1.26 to 14.97, suggesting substantial renal tubular secretion. The median ratio of plasma drug clearance to renal drug clearance approached unity.