Amantadine hydrochloride pharmacokinetics in hemodialysis patients

To study the fate of amantadine hydrochloride in patients with renal failure, we gave 100 mg orally to 12 such patients immediately after hemodialysis. Plasma levels did not decrease between 24 and 44 hours after drug ingestion, suggesting an extremely poor total body clearance. Apparent volume of distribution was 5.1 +/- 0.2 (SEM) L/kg of body weight. Between 44 and 48 hours, as a result of 4 hours of hemodialysis, the mean plasma drug level decreased from 268 to 225 ng/mL (P less than 0.001). Dialyzer clearance was 67.0 +/- 3.9 mL of plasma per minute. The total quantity of drug removed by the dialysis treatment, however, was only 3.9 +/- 0.25 mg. The average half-life of amantadine in eight patients studied while receiving maintenance hemodialysis was 24.3 +/- 2.4 h of dialysis administered over approximately 13 days. Plasma half-life in six nonuremic control subjects was 12.2 +/- 1.6 h. Amantadine is poorly excreted in dialysis patients and has a large volume of distribution. The amount removed by a single dialysis is only a small fraction of the total body store.