EFFECT OF ACUTE EXPERIMENTAL LIVER DYSFUNCTION ON THE PHARMACODYNAMICS OF HEPTABARBITAL IN RATS

The present study aimed to investigate whether the pharmacodynamics of a lipophilic barbiturate, heptabarbital, is altered by liver dysfunction. Heptabarbital was slowly infused i.v., to rats with liver necrosis induced by carbon-tetrachloride, until the rats lost their righting reflex. The concentrations of the drug in serum, brain and CSF were determined in both the diseased animals and solvent-treated controls. Although the concentrations of heptabarbital in the CSF, serum and brain were not significantly different between controls and diseased rats, the total heptabarbital dose required to induce sleep was markedly lower in the diseased animals. Accordingly, the pharmacodynamics of heptabarbital is unaffected in experimental liver dysfunction in rats.