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Pharmacokinetic aspects of elimination from plasma and distribution to brain and liver of barbiturates in rat.

Elimination from plasma and distribution to brain and liver of eight barbituric acid derivatives in J.P. VIII were studied pharmacokinetically after intravenously administration to rat. Plasma concentration time courses of the barbituric acid derivatives were analyzed well with two compartment model. Distribution to brain of the lipid soluble barbituric acid derivatives was so rapid that brain was assigned to compartment I which includes plasma, while the distribution of the acids which have low lipid solubility was slow and the brain was found to be assigned to compartment II, especially for barbital, allobarbital and phenobarbital. On the other hand, liver was assigned to compartment I. As for pharmacokinetic constants, elimination rate constant was found to have a significant regression against lipid solubility (measured as a partition coefficient between CCl4 and pH 7.4 phosphate buffer) except thiopental which belongs to the different series from the other seven barbituric acid derivatives in this paper. On the other hand, distribution rate constants, k12 and k21 were found to have no regression against lipid solubility. From these results, a clue was given to anticipate the plasma concentration and brain level time courses of barbituric acid derivatives from their lipid solubility.