Phenobarbital doses necessary to achieve 'therapeutic' concentrations in children.

Steady-state plasma phenobarbital (PB) concentrations (n = 671) were measured in 438 inpatients. There was a significant relationship between age and PB dose ratio (concentration/dose or 1/clearance) for monotherapy patients; the dose ratio declined in the first year of life, but the dose ratio increased after age 1. The dose ratios were significantly higher in patients receiving PB in combination with other antiepileptic drugs. However, neither sex nor formulations used (tablet, elixir and intravenous) had any influence on the PB dose ratio. The age-dose-concentration relationships indicate that children, especially those under 11 years of age, may require maintenance PB doses more than 5 mg/kg/day to achieve the commonly recommended 'therapeutic' concentration range (10-40 mg/l).