Autoinduction and steady-state pharmacokinetics of carbamazepine and its major metabolites.

1. The effect of carbamazepine (CBZ) dose change on mean plasma concentrations of CBZ, its two metabolites and apparent steady-state clearance was studied in 77 affectively ill patients receiving CBZ at doses of 100-1200 mg day-1. 2. Autoinduction of CBZ metabolism appeared to be complete within 1 week of starting CBZ therapy or dose change, and its degree was linearly related to CBZ daily dose. 3. Curvilinear plots were obtained for steady-state concentrations of CBZ and its -10,11-epoxide metabolite, and for the ratio of CBZ-10,11-epoxide to CBZ level, versus daily dose of CBZ. 4. On the contrary, steady-state concentration of CBZ-10,11-diol increased proportionately with the dose. This indicates that there is no dose dependency in absorption of CBZ, and that dose-dependent autoinduction of CBZ metabolism is the main cause of the curvilinear relationship between dose and steady-state concentration of CBZ and its intermediary metabolite, CBZ-10,11-epoxide.

[An economic evaluation in the pharmacokinetic prediction of preventive carbamazepine therapy]. / Ekonomicheskaia otsenka farmakokineticheskoi prediktsii preventivnoi terapii karbamazepinom.

The paper is concerned with the data of economic evaluation of pharmacokinetic prediction of the individual efficacy of preventive carbamazepin therapy of patients suffering from affective and schizoaffective psychoses. The study was carried out with the aid of the indicators of "direct" and "indirect" expenditures characterizing the efficacy of the use of carbamazepin in the treatment period as compared to the control one, using the pharmacokinetic predictors of the efficacy and without them. The potential economic efficacy of carbamazepin therapy appreciably increases provided the differential diagnostic indications for drug administration are specified. Such a technique of economic analysis of the data of psychopharmacokinetic studies enables their quantitative estimation and determination of economically important research priorities in that area.

[Isolation of substances inhibiting the specific binding of imipramine and serotonin uptake from the brain of the bull]. / Vydelenie veshchestv, ingibiruiushchikhh spetsificheskoe sviazyvanie imipramina i zakhvat serotonina, iz golovnogo mozga byka.

Several fractions that inhibit specific binding of 3H-imipramine and reverse uptake of 3H-serotonin in rat brain synaptosomes were obtained by gel chromatography on Sephadex G-10 from an acidic extract of brain homogenates. The profiles of inhibition of 3H-imipramine specific binding and reverse uptake of 3H-serotonin were found to be in a good agreement. This finding suggests that substances identified in the brain extract may have both types of activities. Further investigations relative to the purification and identification of the substances isolated from bovine brain should be aimed at the search for endogenous ligands for the "imipramine receptor".