Primidone and Phenobarbital, Serum
Monitoring for appropriate therapeutic level
Primidone is used for control of grand mal seizures that are refractory to other antiepileptics and seizures of psychomotor or focal origin.
Primidone is initially dosed in progressively increasing amounts starting with 100 mg at bedtime to 250 mg t.i.d. after 10 days of therapy in adults.
Primidone exhibits a volume of distribution of 0.6 L/kg and a half-life of 8 hours.
When monitoring primidone and phenobarbital levels simultaneously, the specimen should be drawn just before the next dose is administered.
Primidone is not highly protein bound, approximately 10%. Phenobarbital is a metabolite of primidone. Like phenobarbital, there are no known major drug-drug interactions that affect the pharmacology of primidone. Toxicity associated with primidone is primarily due to the accumulation of phenobarbital. Diagnosis and treatment are as described for PBAR / Phenobarbital, Serum.
Children (<5 years): 7.0-10.0 mcg/mL
Adults: 9.0-12.5 mcg/mL
Toxic concentration: > or =15.0 mcg/mL
Infants and children: 15.0-30.0 mcg/mL
Adults: 20.0-40.0 mcg/mL
Toxic concentration: > or =60.0 mcg/mL
At steady-state, which is achieved approximately 2 weeks after therapy is initiated, blood levels of primidone that correlate with optimal response to the drug range from 9.0 to 12.5 mcg/mL for adults and 7.0 to 10.0 mcg/mL for children <5 years of age.
The corresponding levels for phenobarbital are 20 to 40 mcg/mL for adults and 15 to 30 mcg/mL for children <5 years of age.
Dosage adjustment based on blood level information is the best way to obtain optimal response to the drug.
At the same time that the primidone level is monitored, one should also monitor the phenobarbital level, as phenobarbital is a metabolite of primidone.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
Rall TW, Schleifer LS: Drugs effective in the therapy of the epilepsies: primidone. In Goodman and Gilman's The Pharmacological Basis of Therapeutics. Eighth edition. Edited by AG Gilman, TW Rall, AS Nies, P Taylor. New York, Pergamon Press, 1990, pp 446-447