A novel slow-release formulation of lithium carbonate (Carbolithium Once-A-Day) vs. standard Carbolithium: a comparative pharmacokinetic study.

PURPOSE

The purpose of the study was to establish if the administration of a new slow-release formula of lithium carbonate (Carbothium Once-A-Day, 600 mg) administered once-daily could deliver plasma lithium levels during the first 24 hours similar to those obtained with two standard release Carbolithium 300 mg capsules administered 12 hours apart.

PATIENTS AND METHODS

Eighteen healthy subjects of both sexes aged 18 to 55 were randomized to administration of either: [a] a single capsule of Carbolithium Once-A-Day (600 mg), or [b] standard Carbolithium 300 mg b.i.d. Subjects were crossed over following a 15-day washout period. Blood samples were taken 1, 2 4, 6, 8, 10, 12, 16, 20, 24, 36, 48, 72, and 96 hours post-drug administration and analyzed with spectrometry and atomic absorption to detect Li+ plasma concentration.

RESULTS

Data for individual subjects are reported as disjointed numerical values and as individual graphs in the paper. Mean AUC values were 3.01 mM-hours for standard Carbolithium vs. 3.53 mM-hrs for Carbolithium Once-A-Day, and respective mean levels across 96 hours were 0.214 +/- 0.107 vs. 0.252 +/- 0.097 mM. For the first 24 hours, mean AUC values were 2.64 for Carbolithium vs. 3.03 mM-hours for Carbolithium Once-A-Day, and corresponding means were 0.264 vs. 0.303 mM.

CONCLUSION

Carbolithium Once-A-Day was associated with marked reduction of the peak/trough ratio compared to standard release Carbolithium. Given the low therapeutic index of lithium, the maintenance of constant therapeutic concentrations under toxic limits is an essential characteristic of any clinically useful formulation. Furthermore, from the data obtained in the present study it is predicted that, for the majority of patients, a single dose of Carbolithium Once-A-Day will be sufficient to provide therapeutic concentrations of lithium for 24-hour periods. Even the few subjects who will require a double dosage with the Once-A-Day formulation will certainly experience less variations of Li+ plasma concentration throughout the day than would patients receiving rapid release formulations of lithium.