We performed a double-blind trial to investigate the effect of a new aldose reductase inhibitor, ponalrestat, on red blood cell (RBC) sorbitol level in 48 non-insulin dependent diabetics who were orally administered the drug (150 mg, 300 mg, or 600 mg) once daily.
Ponalrestat reduced, in a dose-dependent manner, the increased RBC sorbitol level due to high blood glucose level. The rates of reduction against the predose levels were 16.5% in the 150 mg dose group, 28.8 % in the 300 mg dose group and 43.1 % in the 600 mg dose group. A significant correlation was observed between plasma drug concentration and rate of RBC sorbitol level reduction (r= 0.704).
Although ponalrestat did not affect blood glucose levels, it significantly inhibited the increase in RBC sor itol level in response to the postprandial increase in blood glucose levels. Significant reduction of the RBC sorbitol level remained for 24 hours in the 600 mg dose group. Further, none of the subjects in this study manifested any symptoms or hematobiochemical abnormalities of clinical significance.
Thus, ponalrestat was well tolerated, significantly reduced RBC sorbitol level, and remained effective for 24 hours in the 600 mg dose group.