Effect of tolrestat on red blood cell sorbitol levels in patients with diabetes

Philip Raskin, Julio Rosenstock, Patricia Challis, Steven Ryder, John F. Mullane, Ramona Gonzalez, David Hicks, Theodore Smith, Dushan Dvornik

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


The effect of the aldose reductase inhibitor, tolrestat, on red blood cell (RBC) sorbitol levels was studied in 23 patients with diabetes after oral dosing with tolrestat, 25 or 100 mg b.i.d. The mean (± SE) RBC sorbitol levels (measured 12 hours after the preceding dose) after 3, 7, and 13 days of dosing decreased after both dose levels. After 25 mg tolrestat the RBC sorbitol levels fell from 25.1 ± 4.0 to 20.0 ± 5.7 nmol/gm hemoglobin (21%) and after 100 mg tolrestat the level fell from 26.7 ± 3.7 to 11.4 1.7 nmol/gm hemoglobin (57%; P < 0.001). This latter RBC sorbitol concentration is similar to levels in individuals without diabetes. At both dosage levels the maximum decrease in RBC sorbitol levels occurred after only 3 days of dosing. Tolrestat had no effect on plasma glucose or hemoglobin A, concentrations. The overall mean plasma unbound drug concentration measured 12 hours after 100 mg tolrestat (11.7 ± 3.0 ng/ml; 3.3 × 10-8 mol/L) was similar to the median inhibitory level (3 × 10-8 mol/L) of tolrestat for sorbitol accumulation in human RBCs incubated in a high-glucose medium. Our results demonstrate the systemic bioavailability of tolrestat and its aldose reductase inhibitory activity in erythrocytes of patients with diabetes.

Original languageEnglish (US)
Pages (from-to)625-630
Number of pages6
JournalClinical pharmacology and therapeutics
Issue number6
StatePublished - Dec 1985

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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