Red blood cell sorbitol lowering effects and tolerance of single doses of AL 1576 (HOE 843) in diabetic patients.
The safety and biochemical effects of AL 1576 (HOE 483), a recently developed aldose reductase inhibitor, were evaluated. In a double-blind, placebo-controlled, clinical trial, AL 1576 (HOE 483) was administered to diabetic patients for the first time. Four single, orally administered dose levels were tested, (2, 5, 10, and 20 mg). No clinically important adverse effects were seen in any of the patients. AL 1576 (HOE 483) suppressed red blood cell (RBC) sorbitol concentrations in a dose-related fashion. Also found were statistically significant inverse correlations between the plasma drug concentration and both RBC sorbitol concentrations as well as RBC sorbitol/serum glucose ratios. In single doses up to 20 mg, AL 1576 (HOE 483) is well tolerated and decreases RBC sorbitol, a biochemical marker of pharmacologic activity, in diabetic patients.
Averbuch
M
M
Department of Preventive Medicine, University of Rochester School of Medicine and Dentistry, New York 14642.
Weintraub
M
M
Liao
J C
JC
Brazzell
R K
RK
Dobbs
R E
RE
D000293:Adolescent; D000328:Adult; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004311:Double-Blind Method; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005449:Fluorenes / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006827:Hydantoins / Q000009:adverse effects / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011897:Random Allocation; D013012:Sorbitol / Q000097:blood*; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D005449:Fluorenes; D006827:Hydantoins; D007004:Hypoglycemic Agents; C052241:imirestat; D013012:Sorbitol; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase