Amantadine hydrochloride pharmacokinetics in patients with impaired renal function

To study the disposition of amantadine hydrochloride in patients with impaired renal function, 100 mg was administered orally to 13 patients with creatinine clearances ranging from 48 to 10 ml/min/1.73 m2 body surface area. Six adults with normal renal function served as controls. Plasma half-life averaged 68.5 +/- 9.5 SEM hours in the renal patients (range: 27 to 144), versus 12.6 +/- 1.7 hours in controls. Plasma half-life correlated significantly with serum creatinine (r = 0.8476, P less than 0.001) and serum urea nitrogen levels (r = 0.8791, P less than o.001). Similarly, plasma elimination constant correlated with creatinine clearance/1.73 m2 body surface area (r = 09201, P less than 0.001). Renal amantadine clearance also correlated with creatinine clearance/1.73 m2 body surface area (r = 0.8217, P less than 0.001). However, renal amantadine clearance regularly exceeded creatinine clearance, suggesting that tubular secretion plays a role in the elimination of this drug. Amantadine excretion is decreased in patients with impaired renal function. The amount by which dosage must be reduced can be estimated based on creatinine clearance.