Effect of three different diets on the bioavailability of a sustained release lithium carbonate matrix tablet

Abstract

Background: Food-induced changes on the bioavailability of a sustained release lithium carbonate matrix tablet, which uses an acrylic matrix of Eudragit RSPM as sustaining agent, have been studied in healthy male volunteers. The tablet was developed in our laboratory using conventional technology. Subjects, materials and methods: The study design was a4 x 4 Latin square involving 12 subjects who received a single dose of the tablet while fasting or with a standarized normal, high fat or high fat/high protein meal. Results: The results showed no differences in half-life, renal clearance, Vd beta, AUG, t(max), X-u(infinity), fraction absorbed and MRT. Higher C-max (mg/l) were obtained when the tablet was administered with any kind of meal: 2.09 +/- 0.47 (fast), 2.95 +/- 1.04 (normal diet), 2.64 +/- 0.54 (high fat diet) and 2.87 +/- 0.67 (high fat/high protein diet). The analysis of the ratio C-max/AUC indicated that changes in C-max were more probably due to changes in the rate of absorption. To evaluate if the magnitude of the change could be clinically relevant, C-max and C at 12 hours (dosing interval) were treated by the superposition method in order to establish maximum and minumum concentrations at steady-state. For all the experimental conditions both concentrations would remain in the therapeutic range (4.2 - 10 mg/l or 0.6 - 1.4 mEq/l). Conclusion: The behavior of the formulation is appropriate for a sustained release tablet and fasting or non-fasting state seems not to be a major consideration for bioavailability when deciding on the regimen administration.