The absorption kinetics of barbiturates in rabbits

Abstract The absorption properties of six barbiturates (hexobarbital, pentobarbital, cyclobarbital, amobarbital, allobarbital and barbital) in intact rabbits were studied by means of pharmacokinetic analysis. The absorption rate constant (k a ) was calculated by the Pidgeon and Pitlick method, which does not use data points prior to the maximum plasma concentration (C max ) and therefore is not influenced by errors in the data before the peak concentration. A good correlation was obtained between k a and partition coefficient, suggesting that the absorption properties of barbiturates in intact rabbits are influenced by the lipid solubility of the drugs. Relationships between k a , elimination rate constant (k el ), C max , time of maximum plasma concentration (T max ), and bioavailability (F) were also studied; F and k el might be determinant factors for C max and T max , respectively. The highly lipid-soluble barbiturates are rapidly absorbed from the gastrointestinal tract but are also subject to a first-pass effect, and therefore the extent of absorption decreases with increasing lipid solubility.