Pharmacokinetics of 14C-2-allophanyl-2-allyl -gamma-valero-lactone: a prodrug of proxibarbal in rats.

The pharmacokinetics and metabolism of 2-allophanyl-2-allyl-gamma-valerolactone (AAV) was studied in rats. AAV was partially transformed to proxibarbal and urea, and its urinary elimination was very rapid. AAV becomes widely distributed in tissues and peak concentrations are reached rapidly. A dynamic equilibrium between AAV and proxibarbal was established in the tissues after the AAV concentration had reached its peak. The distribution and kinetics of the two compounds appeared to obey a single compartment system with a half-life of approximately one hour. However, the cerebral proxibarbal half-life was two hours, thus differing from that of all other tissues. The ratio of AAV/proxibarbal in tissues was dependent on tissue pH. With the exception of the brain, this ratio remains constant with time. Proxibarbal release from the brain appeared to result from its back-transformation to AAV. The present data indicate that AAV may be the cerebral prodrug of proxibarbal.