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 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.


METHODS
The study design was a 4 x 4 Latin square involving 12 subjects who received a single dose of the tablet while fasting or with a standardized normal, high fat or high fat/high protein meal.


RESULTS
The results showed no differences in half-lifebeta, renal clearance, Vdbeta, AUC, tmax, Xinfinite(u), fraction absorbed and MRT. Higher Cmax (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 Cmax/AUC indicated that changes in Cmax were more probably due to changes in the rate of absorption. To evaluate if the magnitude of the change could be clinically relevant, Cmax and C at 12 hours (dosing interval) were treated by the superposition method in order to establish maximum and minimum 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).


CONCLUSIONS
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.
Gai
M N
MN
Department of Science and Pharmaceutical Technology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago.
Thielemann
A M
AM
Arancibia
A
A
D018692:Antimanic Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004041:Dietary Fats / Q000008:administration & dosage*; D004044:Dietary Proteins / Q000008:administration & dosage*; D005215:Fasting; D006801:Humans; D016651:Lithium Carbonate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D013607:Tablets
D018692:Antimanic Agents; D003692:Delayed-Action Preparations; D004041:Dietary Fats; D004044:Dietary Proteins; D013607:Tablets; D016651:Lithium Carbonate