Primidone is a minor first-generation
antiepileptic drug, little currently prescribed for this indication, but except marketing authorization, remains a first-line treatment of
essential tremor. Although it is metabolized in phenyl-ethyl-malondamide and
phenobarbital, active metabolites that contribute also to its action,
primidone is not a
prodrug and is active by itself. The rate of conversion of
primidone to
phenobarbital is highly variable according to the subject. Generally accepted therapeutic range for
primidone is between 5 and 10 mg/L (23-46 mmol/L). The therapeutic
drug monitoring (TDM) of
primidone must be accompanied by the determination of
phenobarbital concentrations. The level of proof of the interest of the TDM
primidone was estimated to be "probably useless".
Phenobarbital, a very ancient
anticonvulsant, is much less used today, for the benefit of other more recent compounds. It remains prescribed in neonatology and is one of the compounds used in
status epilepticus. It is a molecule with a long half-life, metabolized in p-hydroxy-
phenobarbital. It is a potent inducer of
CYP3A4. Several side effects, especially drowsiness, are concentration-dependent. Generally accepted therapeutic range for
phenobarbital is between 10 and 40 mg/L (43 - 172 mmol/L), without considering the type of crise. The level of proof of the interest of TDM of
phenobarbital was evaluated as "recommended".