INTRODUCTION/OBJECTIVES: Controlled-release lithium formulations were developed to minimize elevated blood peaks, related to side-effects and intoxications. However, there is little information about the bioavailability of the only controlled-release lithium formulation available in Brazil. The objective of this study was to compare the bioavailability of controlled-release and immediate-release lithium formulations, after single and multiple doses. METHODS: Twelve healthy volunteers received 900 mg of immediate-release or controlled-release lithium carbonate in single or multiple doses during 9 days. After single dose administration, the following parameters were analyzed for each formulation: maximum lithium concentration (Cmax); time to reach Cmax (t max); area under the curve of serum concentration versus time (AUC0-12 and AUC0-<FONT FACE=Symbol>¥</FONT>) and the elimination half-life (t1/2 elim.). After multiple doses, Cmax; t max; AUC0-12; mean (Cmean) and minimum drug concentration (Cmin) and degree of fluctuation (DF) were analyzed. A 90% confidence interval (90%CI) for the ratio between the AUCs for each formulation was constructed. RESULTS/DISCUSSION: Following single dose, the two formulations were bioequivalent; however, they were not after multiple doses. This fact could be a consequence of methodological limitations of lithium level's measurements since, following single dose, these levels could not be detected at time periods 24 and 48h in many volunteers, compromising the calculation of t1/2 elim ,and consequently of the AUC0<FONT FACE=Symbol>-¥</FONT> and the 90%CI to the ratio of these areas. Therefore, the bioequivalence found after single dose may be an unreliable result.
Lithium carbonate; Bioavailability; Dosage forms; Single dose; Doses repetition; Healthy man
