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

Background: Food-induced changes on the bioavailability of a sustained rele ase lithium carbonate matrix tablet, which uses an acrylic matrix of Eudrag it RSPM as sustaining agent, have been studied in healthy male volunteers. The tablet was developed in our laboratory using conventional technology. S ubjects, materials and methods: The study design was a4 x 4 Latin square in volving 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. Resul ts: The results showed no differences in half-life, renal clearance, Vd bet a, 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 di et) and 2.87 +/- 0.67 (high fat/high protein diet). The analysis of the rat io C-max/AUC indicated that changes in C-max were more probably due to chan ges in the rate of absorption. To evaluate if the magnitude of the change c ould be clinically relevant, C-max and C at 12 hours (dosing interval) were treated by the superposition method in order to establish maximum and minu mum concentrations at steady-state. For all the experimental conditions bot h 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 t o be a major consideration for bioavailability when deciding on the regimen administration.