Pharmacokinetics and relative bioavailability of vinylbital in man after oral and rectal administration.

A sensitive and specific method for the quantitative determination of 5-vinyl-5-(1-methylbutyl)-barbituric acid (vinylbital) in plasma was developed, by using gas chromatography with alkali flame ionization detection. The method is suitable for measuring vinylbital plasma levels in man after administration of therapeutic doses. The pharmacokinetics and relative bioavailability of vinylbital after oral and rectal administration were studied in man. Tablets (Bykonox) containing 150 mg vinylbital, were used for the oral experiments and suppositories (Suppoptanox, polyethylene glycol base) containing 200 mg vinylbital, were used for rectal administration. Six volunteers participated in a cross-over way in the study. Vinylbital plasma concentrations were determined at regular intervals after drug administration. Absorption and elimination of vinylbital appeared to occur according to a single first-order process and the plasma concentrations were fitted by computer according to the equation intrinsic to the one-compartment open model after oral or rectal administration. The lag time was shorter for the suppository than for the tablet, whereas the absorption rate was faster for the tablet (mean absorption half-life 0.24 h compared with 0.64 h for the suppository). The elimination half-life of vinylbital varied from 17.6 to 33.5 h, with a mean value of 23.5 h for oral administration and 23.8 h for rectal administration. The half-lives were not considerably different on the two occasions for the individual volunteers. The average bioavailability of vinylbital for the suppository, relative to the tablet, was approximately 93%. Three volunteers collected their urine during 3--4 days after administration of a tablet. Unchanged vinylbital was determined and approximately 1.6% of the administered dose was excreted as unchanged drug. Some preliminary experiments of repetive vinylbital administration showed that self-induction of metabolism did not occur.