To the Editor.
—Atkinson et al,1 in a previous issue of the Archives, made the interesting observation that 48% of 78 mentally handicapped children and adults experienced apparent side effects while ingesting amantadine hydrochloride for influenza A prophylaxis and commented that serum amantadine concentrations were two to three times higher than expected. Serum amantadine concentrations, six to eight hours after the last dose, on day 28 of drug ingestion, averaged 1991 and 1358 ng/mL in eight and six patients, respectively. No clear explanation for these observations was evident; the patients were 5 to 64 years of age, had normal serum creatinine concentrations, and were ingesting 6.6 mg/kg/d of the drug, within the manufacturer's recommended dose range. To determine whether pharmacokinetic factors might account in part for their observation, we reexamined unpublished data from our study of amantadine plasma concentrations (Cp) in 15 young adults ingesting 50, 200, or 300