Clinical Pharmacology of Phenobarbital in Infants and Children

Phenobarbital inhibits seizures by potentiation of synaptic inhibition through an action on the GABAA receptor. Phenobarbital is an effective agent for generalized tonic-clonic focal-to-bilateral tonic-clonic and focal seizures. Phenobarbital may be administered orally or intravenously and following oral dosing phenobarbital is completely absorbed. In infants, seizures are controlled by an intravenous loading dose of 20 mg/kg followed by a maintenance dose of 4 mg/kg once-daily. In children, the treatment of all forms of epilepsy, except for typical absence seizures, consists in an oral phenobarbital and the status epilepticus is treated with intravenous phenobarbital and treatments consist in a loading dose followed by a maintenance dose. Phenobarbital induces several CYPs, UGT1A1, and CYP2B and CYP3A genes. In newborns and children, the elimination half-life is 46.9 hours and the distribution volume is 0.49 L/kg. In children with severe falciparum malaria and convulsions, the distribution volume is 0.79 L/kg. The treatment and trials with phenobarbital have been studied and phenobarbital interacts with drugs. Phenobarbital is transported into the human brain where reaches therapeutic concentrations and phenobarbital freely crosses the human placenta. Following therapeutic treatment with phenobarbital to lactating women, the concentrations of phenobarbital in the breast-milk are few µg/ml suggesting that phenobarbital poorly migrates into the breast-milk. The aim of this study is to review the published data of phenobarbital dosing, pharmacokinetics, treatment, and trials in infants and children, and the phenobarbital metabolism, phenobarbital transport in the human brain, placental transfer of phenobarbital, and phenobarbital migration into the breast-milk.