Single-dose kinetics of primidone in acute viral hepatitis

The pharmacokinetics of primidone (PRM) after oral administration of a single 500 mg dose was studied in 7 patients with acute viral hepatitis and 7 healthy control subjects. The elimination half-life and the apparent clearance of unchanged PRM in the patients were 18.0 +/- 3.1 h and 42 +/- 14 ml X h-1 X kg-1, respectively (mean +/- SD) and did not differ significantly from the values in the controls (half-life 17.0 +/- 2.4 h; clearance 35 +/- 8 ml X h-1 X kg-1). The metabolite phenylethylmalonamide (PEMA) was detected in the serum of all normal subjects within 2-24 h. By contrast, serum levels of this metabolite were undetectable (less than 2 mumol/1) in all but one of the patients. Serum levels of phenobarbital (PB) remained below the limit of detection (less than 2 mumol/1) in all subjects. The findings indicate that accumulation of PRM with its attendant toxicity is unlikely to occur in epileptic patients who develop acute viral hepatitis, despite evidence that the metabolism of the drug is affected by this condition. The possibility of impaired conversion to PB and its implications are discussed.