Absorption and disposition kinetics of lithium carbonate following administration of conventional and controlled release formulations

Abstract

The absorption and disposition kinetics of lithium carbonate administered to eight healthy volunteers in two dosage forms were studied. A conventional immediate release tablet and a controlled release preparation, developed in our laboratory and containing the drug into a hydrophilic matrix, were employed in the study. Lithium carbonate confers upon the body the distinct characteristics of a two-compartment open model with a mean slow disposition rate constant (beta) of 0.0435 h-1 +/- 0.0086 SD, corresponding to a mean biological half-life of 16.49 h +/- 2.95 SD. The mean half-life of the distributory alpha-phase was 1.40 h +/- 0.27 SD. The apparent volume of distribution (Vdarea) was 0.539 l kg-1 +/- 0.130 SD and the volume of the central compartment (Vl) was 0.224 l/kg-1 +/- 0.066 SD, about one half that of the volume at steady state (Vdss) which was 0.445 l/kg-1 +/- 0.106 SD. Total body clearance (ClB) was 0.0241 l/kg-1 h +/- 0.0102 SD. The administration of the controlled release preparations to the same subjects gave the expected smooth serum lithium concentration curves. Maximum serum concentration (Cmax) was 22% lower and the time at which this concentration was attained (tpeak) was delayed from 1.44 h to 4.25 h when compared with the conventional tablet. Bioavailability, estimated as the total amount of lithium excreted in the urine, was 90.2 for the controlled release preparation and 94.5 for the immediate release tablet.