Phenobarbital Pharmacokinetics in Infants Using Saliva as a Biologic Fluid

Abstract

Objective: To determine the pharmacokinetic parameters of phenobarbital in infants, using saliva as a biologic fluid, and to correlate the parameters obtained from saliva data with those obtained from plasma data. Design: A prospective, randomized study. Setting: Hospitalized patients at the Medical Center Pereira Rossell, a pediatric hospital in Montevideo, Uruguay. Patients: Sixteen infants with seizure disorders were included in the study. None of them was treated with other medications. Interventions: A direct intravenous loading dose of phenobarbital 10 mg/kg was administered, followed by a maintenance dosage of 5 mg/kg/d (once- or twice-daily dosing) given 12 hours after the loading dose. Main Outcome Measures: Saliva and plasma samples were obtained 6 and 12 hours after the loading dose and 3 days after the initiation of the maintenance dose (trough sample): the samples were analyzed by HPLC and the elimination half-life (t1/2), the volume of distribution (Vd), and the percentage of unbound drug in plasma (UDP) were calculated. Results: The t1/2 obtained from plasma and saliva data was 30 hours; the Vd was 0.73 L/kg from plasma data and 2.4 L/kg from saliva data; and the UDP was 75 percent. Trough concentrations showed no significant difference between treatments. Conclusions: Saliva is a useful biologic fluid to determine phenobarbital pharmacokinetic parameters, mainly in pediatric patients. Moreover, a single daily dose of phenobarbital is sufficient to obtain therapeutic concentrations.