Pharmacokinetics, pharmacodynamics, tolerability, and safety of a novel sorbitol dehydrogenase inhibitor in healthy participants

Journal of Clinical Pharmacology

Volumn 50, Issue 5, 2010, Pages 521-530

  Landau, Zohar ^a   Novotny, Mark J ^a   Preston, Gregory M ^a   Wright, Kathryn ^a   Freeman, Thomas ^a   Haiqing Dai, ^a   Thompson, John ^a   Oates, Peter J ^a   Calle, Roberto A ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

Aldose reductase; Diabetic complications; Fructose; Polyol pathway; Sorbitol

Indexed keywords

ANTIDIABETIC AGENT; BIOLOGICAL MARKER; CP 642931; ENZYME INHIBITOR; IDITOL DEHYDROGENASE; PLACEBO; SORBITOL; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CREATINE KINASE BLOOD LEVEL; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG DETERMINATION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ENZYME ACTIVITY; ENZYME INHIBITION; FASCICULATION; FEMALE; FOLLOW UP; HUMAN; KIDNEY FUNCTION TEST; LIVER FUNCTION TEST; MAJOR CLINICAL STUDY; MALE; MUSCLE DENERVATION; MUSCLE FATIGUE; MUSCLE SPASM; MUSCLE WEAKNESS; MYALGIA; NEUROPATHY; PHARMACODYNAMICS; PHARMACOKINETICS; PHASE 1 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SINGLE DRUG DOSE; THYROID FUNCTION TEST; TOXIC MYOPATHY; TREMOR;

ADMINISTRATION, ORAL; ADULT; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; ENZYME INHIBITORS; FEMALE; FOLLOW-UP STUDIES; HALF-LIFE; HUMANS; L-IDITOL 2-DEHYDROGENASE; MALE; MIDDLE AGED; SORBITOL; TIME FACTORS; YOUNG ADULT;

EID: 77951189315     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270009336354     Document Type: Article

References (29)

1. Resnick HE, Foster GL, Bardsley J., Ratner RE Achievement of American Diabetes Association clinical practice recommendations among U.S. adults with diabetes, 1999-2002: the National Health and Nutrition Examination Survey. Diabetes Care. 2006 ; 29: 531-537.
2. Oates PJ Polyol pathway and diabetic peripheral neuropathy. Int Rev Neurobiol. 2002 ; 50: 325-392.
3. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005 ; 54: 1615-1625.
4. Williamson JR, Ido Y., Kilo C., Tilton RG Hyperglycemic Pseudohypoxia and Diabetes Complications: Sorbitol Pathway-Generated NADHc Mediates Diabetes Complications. Alexandria, VA: American Diabetes Association ; 2006.
5. Barnett PA, Gonzalez RG, Chylack LT Jr, Cheng HM The effect of oxidation on sorbitol pathway kinetics. Diabetes. 1986 ; 35: 426-432.
6. Ido Y. Pyridine nucleotide redox abnormalities in diabetes. Antioxid Redox Signal. 2007 ; 9: 931-942.
7. Sarges R., Oates PJ Aldose reductase inhibitors: recent developments. Prog Drug Res. 1993 ; 40: 99-161.
8. Schmidt RE, Dorsey DA, Beaudet LN, et al. A potent sorbitol dehydrogenase inhibitor exacerbates sympathetic autonomic neuropathy in rats with streptozotocin-induced diabetes. Exp Neurol. 2005 ; 192: 407-419.
9. Geisen K., Utz R., Grotsch H., Lang HJ, Nimmesgern H. Sorbitol-accumulating pyrimidine derivatives. Arzneimittelforschung. 1994 ; 44: 1032-1043.
10. Tilton RG, Chang K., Nyengaard JR, Van den Enden M., Ido Y., Williamson JR Inhibition of sorbitol dehydrogenase: effects on vascular and neural dysfunction in streptozocin-induced diabetic rats. Diabetes. 1995 ; 44: 234-242.
11. Chu-Moyer MY, Ballinger WE, Beebe DA, et al. Orally-effective, long-acting sorbitol dehydrogenase inhibitors: synthesis, structure-activity relationships, and in vivo evaluations of novel heterocycle-substituted piperazino-pyrimidines. J Med Chem. 2002 ; 45: 511-528.
12. Cameron NE, Cotter MA, Basso M., Hohman TC Comparison of the effects of inhibitors of aldose reductase and sorbitol dehydrogenase on neurovascular function, nerve conduction and tissue polyol pathway metabolites in streptozotocin-diabetic rats. Diabetologia. 1997 ; 40: 271-281.
13. Obrosova IG, Fathallah L., Lang HJ, Greene DA Evaluation of a sorbitol dehydrogenase inhibitor on diabetic peripheral nerve metabolism: a prevention study. Diabetologia. 1999 ; 42: 1187-1194.
14. Schmidt RE, Dorsey DA, Beaudet LN, Plurad SB, Williamson JR, Ido Y. Effect of sorbitol dehydrogenase inhibition on experimental diabetic autonomic neuropathy. J Neuropathol Exp Neurol. 1998 ; 57: 1175-1189.
15. Hayashi R., Hayakawa N., Makino M., et al. Changes in erythrocyte sorbitol concentrations measured using an improved assay system in patients with diabetic complications and treated with aldose reductase inhibitor. Diabetes Care. 1998 ; 21: 672-673.
16. Asano T., Saito Y., Kawakami M., Yamada N., Sekino H., Hasegawa S. Erythrocytic sorbitol contents in diabetic patients correlate with blood aldose reductase protein contents and plasma glucose levels, and are normalized by the potent aldose reductase inhibitor fidarestat (SNK-860). J Diabetes Complications. 2004 ; 18: 336-342.
17. Nakano I., Tsugawa T., Shinohara R., et al. Urinary sorbitol measurement and the effect of an aldose reductase inhibitor on its concentration in the diabetic state. J Diabetes Complications. 2003 ; 17: 337-342.
18. Medina C., Vaca G., Rios J., et al. Screening for red blood cell sorbitol dehydrogenase deficiency in patients with diabetes or cataracts. Ophthalmic Paediatr Genet. 1987 ; 8: 197-202.
19. World Medical Association Declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. JAMA. 1997 ; 277: 925-926.
20. Küry D., Keller U. Trimethylsilyl-O-methyloxime derivatives for the measurement of [6,6-2H2]-D-glucose-enriched plasma samples by gas chromatography-mass spectrometry. J Chromatogr. 1991 ; 572 (1-2). 302-306.
21. Demaine AG Polymorphisms of the aldose reductase gene and susceptibility to diabetic microvascular complications. Curr Med Chem. 2003 ; 10: 1389-1398.
22. Oates PJ, Mylari BL Aldose reductase inhibitors: therapeutic implications for diabetic complications. Expert Opin Investig Drugs. 1999 ; 8: 2095-2119.
23. Amano S., Yamagishi S., Kato N., et al. Sorbitol dehydrogenase overexpression potentiates glucose toxicity to cultured retinal pericytes. Biochem Biophys Res Commun. 2002 ; 299: 183-188.
24. Amano S., Yamagishi S., Koda Y., et al. Polymorphisms of sorbitol dehydrogenase (SDH) gene and susceptibility to diabetic retinopathy. Med Hypotheses. 2003 ; 60: 550-551.
25. Oates PJ Aldose reductase, still a compelling target for diabetic neuropathy. Current Drug Targets. 2008 ; 9: 14-36.
26. Engerman RL, Kern TS, Larson ME Nerve conduction velocity in dogs is reduced by diabetes and not by galactosemia. Metabolism. 1990 ; 39: 638-640.
27. Schmidt RE Neuropathology and pathogenesis of diabetic autonomic neuropathy. Int Rev Neurobiol. 2002 ; 50: 257-292.
28. Shin YS, Rieth M., Endres W., Haas P. Sorbitol dehydrogenase deficiency in a family with congenital cataracts. J Inherit Metab Dis. 1984 ; 7 (suppl 2). 151-152.
29. Vaca G., Ibarra B., Bracamontes M., et al. Red blood cell sorbitol dehydrogenase deficiency in a family with cataracts. Hum Genet. 1982 ; 61: 338-341.