Ty Vo and Kristine B Marcus

To request full article click here.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and safety of ranirestat, an oral aldose reductase inhibitor with a unique chemical structure, as treatment of diabetic sensorimotor polyneuropathy in patients with diabetes mellitus.

DATA SOURCES: Primary literature and review articles were identified by searching MEDLINE (1950–June 2008), EMBASE (1991–June 2008), International Pharmaceutical Abstracts (1970–June 2008), and Google Scholar using the key terms ranirestat, AS-3201, SX-3030, aldose reductase inhibitors, diabetes mellitus, and peripheral neuropathy. Additional articles were identified from the bibliographies of the obtained literature.

Study Selection and Data Extraction: Reviewed literature was restricted to available English-language articles. Preclinical and clinical trials were reviewed. One Phase 2 clinical trial and its extension study were identified. No data have yet been reported from Phase 3 trials that were conducted between 2004 and 2006.

Data Synthesis: Ranirestat is a selective and reversible inhibitor of aldose reductase. Nerve damage is reduced by inhibiting this key enzyme in the polyol pathway, thus preventing the accumulation of sorbitol and fructose. Ranirestat has been compared with placebo in randomized, double-blind, controlled trials. Improvement in nerve function, sensation, and clinical grading scale were noted. Ranirestat was reported to be well tolerated.

CONCLUSIONS: Ranirestat may offer a clinical advantage over current treatment modalities as the first agent to address one factor in the underlying cause of diabetic sensorimotor polyneuropathy. Further studies should be done on safety, efficacy, tolerability, and quality of life to determine how successful this agent will be in the treatment of diabetic sensorimotor polyneuropathy.

J Pharm Technol 2008;24:340-4.
ACPE Universal Program Number: 407-000-08-056-H01-P (Pharmacists); 407-000-08-056-H01-T (Technicians)