In man, amantadine is readily absorbed, passes the blood-brain barrier and appears in the saliva and nasal secretions. The drug can be detected in the blood and cerebrospinal fluid at relatively low, but dose-related, levels. No evidence of metabolites has been found and 90% or more of the dose can be recovered in the urine unchanged.
After oral administration of a single dose of 100 mg, maximum blood levels are reached in approximately 4 hours, based on mean time of the peak urinary excretion rate; the peak excretion rate is approximately 5 mg/hour; the mean half-life of the excretion rate approximates 15 hours.
Compared with otherwise healthy adult individuals, the clearance of amantadine is significantly reduced in adult patients with renal insufficiency. The elimination half-life increases 2 to 3 fold when creatinine clearance is less than 40 mL/min/1.73m2 and averages 8 days in patients on chronic maintenance hemodialysis.
The renal clearance of amantadine is reduced and plasma levels are increased in otherwise healthy elderly patients age 65 years and older. The drug plasma levels in elderly patients receiving 100 mg daily have been reported to approximate those determined in younger adults taking 200 mg daily. Whether these changes are due to the normal decline in renal function or other age factors is not known.
Amandatine is useful in the treatment of Parkinson's syndrome and in the short-term management of drug-induced extrapyramidal symptoms.
In Parkinson's syndrome, amantadine has been used alone and in combination with anticholinergic antiparkinsonian drugs and with levodopa. The final therapeutic benefit seen with amantadine is significantly less than that seen with levodopa. The maximal therapeutic benefit to be obtained with amantadine is usually seen within 1 week. However, initial benefits may diminish with continued dosing.
Amantadine is useful as an adjunct in patients who do not tolerate optimal doses of levodopa alone or in combined therapy with a decarboxylase inhibitor. In these patients, the addition of amantadine may result in better control of Parkinson's syndrome and may help to smooth out fluctuations in performance.
The comparative efficacy of amantadine and anticholinergic antiparkinson drugs has not yet been established. When amantadine or anticholinergic antiparkinsonian drugs are each used with marginal benefit, concomitant use may permit the same degree of control, often with a lower dose of the anticholinergic medication.
Amantadine is effective in reducing severity or abolishing drug-induced extrapyramidal reactions including parkinsonism syndrome, dystonia and akathisia. It is not effective in the management of tardive dyskinesia.
Although anticholinergic-type side effects have been noted when used in patients with drug-induced extrapyramidal reactions, there appears to be a lower incidence of these side effects than that observed with anticholinergic antiparkinsonian drugs.
Antiparkinsonian agents should not usually be used prophylactically during neuroleptic administration. However, they may be given when needed to suppress extrapyramidal symptoms. Therefore, amantadine may be used in the management of extrapyramidal symptoms which cannot be controlled by reduction of neuroleptic dosage, but should be discontinued as soon as it is no longer required. Amantadine should be withdrawn after a period of time to determine whether there is recrudescence of extrapyramidal symptoms.
