PHARMACOKINETICS OF BUTOBARBITAL AFTER SINGLE AND MULTIPLE ORAL DOSES IN MAN

A method is described for the assay of therapeutic levels of butobarbital (5-ethyl-5-n-butylbarbituric acid) in human plasma, which involves a single extraction step followed by gas chromatography with alkali flame ionization detection. The pharmacokinetics of butobarbital were studied in 5 healthy volunteers after oral administration of 200 mg. Plasma concentrations were determined at regular intervals up to 96 h and the data were fitted by non-linear, least squares regression analysis according to 1-compartment kinetics. The average lag time was 0.11 h and the absorption half-life 0.21 h. The elimination half-life varied from 33.6-41.5 h with an average of 37.5 h. Four of the volunteers participated in a study of multiple dosing (every 24 h) during which substantial accumulation of butobarbital was observed. The elimination half-life after termination of drug administration had decreased to about 20-25% of its initial value, probably because of enzyme induction. Butobarbital could not be regarded as a suitable drug for treatment of insomnia, since CNS depressant effects were likely to persist into the following day. Repeated administration of butobarbital should be avoided and its incidental use restricted to patients who require day-time sedation.