Bioavailability of metformin. Comparison of solution, rapidly dissolving tablet, and three sustained release products

To study the bioavailability of metformin from aqueous solution (A), a rapidly dissolving tablet (B), and three sustained release products (D, C, E), a single oral dose (1.0 g) of these products was administered to six healthy volunteers in a randomized cross-over study. Plasma levels of metformin were followed up to 10 h and excretion into urine up to 48 h after the dose. The peak plasma levels after A and B were similar and significantly (p less than 0.05) higher than after C, D and E. The AUC was significantly (p less than 0.05) higher with A than with other products. The recovery of metformin in urine was 37%, 33%, 25%, 28% and 29% of the dose after A, B, C, D and E, respectively. The values of A and B were significantly (p less than 0.05) higher than those of C, D and E. The renal clearance of metformin was similar after all the products, averaging 518 +/- 16 (SE) ml/min. The terminal elimination half-life on the basis of urinary excretion rate data averaged 12.6 +/- 0.6 h with no significant difference between the products. The bioavailability on the basis of urinary excretion of metformin showed a significant (p less than 0.05) positive correlation to the dissolution rate of the products in vitro. Thus, the bioavailability of metformin even from aqueous solution and rapidly dissolving tablets is relatively low and further deteriorates when metformin is administered as sustained release products. The bioavailability of the three sustained release products studied was similar.