Amantadine kinetics in healthy elderly men: Implications for influenza prevention

Abstract

Amantadine kinetics were investigated in 10 healthy elderly men 60-76 yr old. A dose that would yield the same trough steady-state plasma amantadine concentration (Cpss; 300 ng/ml) as a 200 mg/day dose taken by young healthy adults; this dose prevents influenza A virus infection and is well tolerated by this population. With a 1-compartment open model, kinetic parameters were calculated after a single dose of 25, 50, or 75 mg or the same dose twice a day for 10.5 days. Peak concentration occurred 4.0-8.0 h after dosing, but the calculated AUC [area under the concentration] was proportional to dose, indicating that relative bioavailability was independent of dose. This was supported by recovery of 88% of the single doses in urine. No change in apparent volume of distribution was found. Log trough Cpss increased with dose. Trough Cpss varied < 300% for equivalent doses. There was 1st-order elimination of drug from plasma, with a median t1/2 [half time] of 28.9 h (range 18.5-45.0 h), and elimination was independent of dose and creatinine clearance. The median ratio of renal amantadine clearance to creatine clearance was 2.07 (range 0.64-4.20), suggesting renal tubular secretion. Compared to data from healthy young adults, the t1/2 was doubled and renal drug clearance was diminished in elderly men. To achieve the target trough Cpss of 300 ng/ml, healthy older men must take amantadine at a dose of 1.4 mg/kg per day, and it is suggested that this is a rational dose for evaluation of efficacy and safety for influenza A prophylaxis in this population.