Preclinical species and human disposition of PF-04971729, a selective inhibitor of the sodium-dependent glucose cotransporter 2 and clinical candidate for the treatment of type 2 diabetes mellitus

Drug Metabolism and Disposition

Volumn 39, Issue 9, 2011, Pages 1609-1619

  Kalgutkar, Amit S ^a   Tugnait, Meera ^a   Zhu, Tong ^a   Kimoto, Emi ^a   Miao, Zhuang ^a   Mascitti, Vincent ^a   Yang, Xin ^a   Tan, Beijing ^a   Walsky, Robert L ^a   Chupka, Jonathan ^a   Feng, Bo ^a   Robinson, Ralph P ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 [4 CHLORO 3 (4 ETHOXYBENZYL)PHENYL] 1 HYDROXYMETHYL 6,8 DIOXABICYCLO[3.2.1]OCTANE 2,3,4 TRIOL; ANTIDIABETIC AGENT; CARBON 14; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; DRUG METABOLITE; GLUCURONOSYLTRANSFERASE 1A9; GLUCURONOSYLTRANSFERASE 2B7; METFORMIN; PF 04971729; RECOMBINANT ENZYME; SODIUM GLUCOSE COTRANSPORTER 2; UNCLASSIFIED DRUG;

ALLOMETRY; ANIMAL CELL; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; CRYOPRESERVATION; DISTRIBUTION VOLUME; DOG; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DISPOSITION; DRUG DISTRIBUTION; DRUG GLUCURONIDATION; DRUG HALF LIFE; DRUG HYDROXYLATION; DRUG METABOLISM; DRUG TRANSFORMATION; ENZYME INHIBITION; FEMALE; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; LIVER CELL; LIVER MICROSOME METABOLISM; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PHENOTYPE; PLASMA CLEARANCE; PREDICTION; PRIORITY JOURNAL; RAT; SPECIES DIFFERENCE; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADMINISTRATION, ORAL; ADULT; ANIMALS; BICYCLO COMPOUNDS, HETEROCYCLIC; BIOLOGICAL AVAILABILITY; BIOTRANSFORMATION; CACO-2 CELLS; CROSS-OVER STUDIES; CYTOCHROME P-450 ENZYME SYSTEM; DOGS; DRUG EVALUATION, PRECLINICAL; FEMALE; GLUCURONOSYLTRANSFERASE; HEK293 CELLS; HEPATOCYTES; HUMANS; INTESTINAL ABSORPTION; MALE; MICROSOMES, LIVER; MIDDLE AGED; PROTEIN BINDING; RATS; RATS, SPRAGUE-DAWLEY; SODIUM-GLUCOSE TRANSPORT PROTEINS; YOUNG ADULT;

CANIS FAMILIARIS; RATTUS;

EID: 80051983395     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.111.040675     Document Type: Article

References (40)

1. Abdul-Ghani MA and DeFronzo R.A. (2008) Inhibition of renal glucose reabsorption: A novel strategy for achieving Glucose control in type 2 diabetes mellitus. Endocr Pract 14:782-790.
2. +-glucose transporter inhibitor, improves hyperglycemia in streptozotocin-induced diabetic rats. Metabolism 49:990-995.
3. Aires I and Calado J. (2010) BI- 10773, a sodium- 10773, a sodiumGlucose cotransporter 2 inhibitor for the potential oral treatment of type 2 diabetes mellitus. Curr Opin Investig Drugs 11:1182-1190.
4. Bachmakov I., Glaeser H., Endress B., Mörl F., König J, and Fromm M.F. (2009) Interaction of β- Blockers with the renal uptake transporter OCT2. Diabetes Obes Metab 11:1080-1083.
5. Bailey C.J., Gross J.L., Pieters A., Bastien A, and List J.F. (2010) Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double- Blind, placebo- Blind, placeboControlled trial. Lancet 375:2223-2233.
6. Bołdys A and Okopień B. (2009) Inhibitors of type 2 sodium glucose co- Transporters- TransportersA new strategy for diabetes treatment. Pharmacol Rep 61:778-784.
7. Chen Y., Li S., Brown C., Cheatham S., Castro R.A., Leabman M.K., Urban T.J., Chen L., Yee S.W., Choi J.H., et al. (2009) Effect of genetic variation in the organic cation transporter 2 on the renal elimination of metformin. Pharmacogenet Genomics 19:497-504.
8. Chiou WL and Barve A. (1998) Linear correlation of the fraction of oral dose absorbed of 64 drugs between humans and rats. Pharm Res 15:1792-1795. (Pubitemid 28524594)
9. DeFronzo R.A. (1988) Lilly Lecture 1987: The triumvirate: β- Cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37:667-687.
10. Defronzo R.A. (2009) Banting Lecture. From the triumvirate to the ominous octet: A new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 58:773-795.
11. Elsby R., Surry D.D., Smith VN, and Gray A.J. (2008) Validation and application of Caco- 2 assays for the in vitro evaluation of development candidate drugs as substrates or inhibitors of P- 2 assays for the in vitro evaluation of development candidate drugs as substrates or inhibitors of PGlycoprotein to support regulatory submissions. Xenobiotica 38:1140-1164.
12. Frederick K.S., Maurer T.S., Kalgutkar A.S., Royer L.J., Francone O.L., Winter S.M., Terra S.G., Chen D, and Gao X. (2009) Pharmacokinetics, disposition and lipid-modulating activity of 5-{2-[4-(3,4-difluorophenoxy)-phenyl]- ethylsulfamoyl}-2-methyl-benzoic acid, a potent and subtype-selective peroxisome proliferator-activated receptor α agonist in preclinical species and human. Xenobiotica 39:766-781.
13. Fujimori Y., Katsuno K., Nakashima I., Ishikawa-Takemura Y., Fujikura H, and Isaji M. (2008) Remogliflozin etabonate, in a novel category of selective low- Affinity sodium glucose cotransporter (SGLT2) inhibitors, exhibits antidiabetic efficacy in rodent models. J Pharmacol Exp Ther 327:268-276.
14. Hosea N.A., Collard W.T., Cole S., Maurer T.S., Fang R.X., Jones H., Kakar S.M., Nakai Y., Smith B.J., Webster R., et al. (2009) Prediction of human pharmacokinetics from preclinical information: Comparative accuracy of quantitative prediction approaches. J Clin Pharmacol 49:513-533.
15. Kalgutkar A.S., Frederick K.S., Chupka J., Feng B., Kempshall S., Mireles R.J., Fenner KS, and Troutman M.D. (2009) N-(3,4-Dimethoxyphenethyl)-4-(6,7- dimethoxy-3,4-dihydroisoquinolin-2[1H]-yl)-6,7-dimethoxyquinazolin-2-amine (CP-100,356) as a "chemical knock-out equivalent" to assess the impact of efflux transporters on oral drug absorption in the rat. J Pharm Sci 98:4914-4927.
16. +/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. J Clin Invest 93:397-404.
17. Kasichayanula S., Chang M., Hasegawa M., Liu X., Yamahira N., LaCreta F.P., Imai Y, and Boulton D.W. (2011) Pharmacokinetics and pharmacodynamics of dapagliflozin, a novel selective inhibitor of sodium-glucose co- Glucose coTransporter type 2, in Japanese subjects without and with type 2 diabetes mellitus. Diabetes Obes Metab 13:357-365.
18. Katsuno K., Fujimori Y., Takemura Y., Hiratochi M., Itoh F., Komatsu Y., Fujikura H, and Isaji M. (2007) Sergliflozin, a novel selective inhibitor of low- Affinity sodium glucose cotransporter (SGLT2), validates the critical role of SGLT2 in renal glucose reabsorption and modulates plasma glucose level. J Pharmacol Exp Ther 320:323-330. (Pubitemid 46025747)
19. Kimura N., Masuda S., Tanihara Y., Ueo H., Okuda M., Katsura T, and Inui K. (2005) Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet 20:379-386.
20. King H., Aubert RE, and Herman W.H. (1998) Global burden of diabetes, 1995- 2025: prevalence, numerical estimates, and projections. Diabetes Care 21:1414-1431. (Pubitemid 28405191)
21. List J.F., Woo V., Morales E., Tang W, and Fiedorek F.T. (2009) Sodium- Glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care 32:650-657.
22. Mascitti V., Maurer T.S., Robinson R.P., Bian J., Boustany-Kari C.M., Brandt T., Collman B.M., Kalgutkar A.S., Klenotic M.K., Leininger M.T., et al. (2011) Discovery of a clinical candidate from the structurally unique dioxa- Bicyclo[3.2.1]octane class of sodium- Bicyclo[3.2.1]octane class of sodiumDependent glucose cotransporter 2 inhibitors. J Med Chem 54:2952-2960.
23. Meng W., Ellsworth B.A., Nirschl A.A., McCann P.J., Patel M., Girotra R.N., Wu G., Sher P.M., Morrison E.P., Biller S.A., et al. (2008) Discovery of dapagliflozin: a potent, selective renal sodium- Dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. J Med Chem 51:1145-1149. (Pubitemid 351480378)
24. Mokdad A.H., Ford E.S., Bowman B.A., Dietz W.H., Vinicor F., Bales VS, and Marks J.S. (2003) Prevalence of obesity, diabetes, and obesity- Related health risk factors, 2001. JAMA 289:76 -79.
25. Nair S and Wilding J.P. (2010) Sodium glucose cotransporter 2 inhibitors as a new treatment for diabetes mellitus. J Clin Endocrinol Metab 95:34-42.
26. Neumiller J.J., White J.R. Jr, and Campbell R.K. (2010) Sodium-glucose co- Glucose coTransport inhibitors: progress and therapeutic potential in type 2 diabetes mellitus. Drugs 70:377-385.
27. +-glucose cotransporters, may provide a novel approach to treating diabetes. Diabetes 48:1794-1800.
28. Pacifici GM and Viani A. (1992) Methods of determining plasma and tissue binding of drugs. Pharmacokinetic consequences. Clin Pharmacokinet 23:449-468.
29. +/nucleoside cotransporter. A member of the SGLT family. J Biol Chem 267:3557-3560.
30. Robinson R.P., Mascitti V., Boustany-Kari C.M., Carr C.L., Foley P.M., Kimoto E., Leininger M.T., Lowe A., Klenotic M.K., Macdonald J.I., et al. (2010) C- Aryl glycoside inhibitors of SGLT2: exploration of sugar modifications including C- Aryl glycoside inhibitors of SGLT2: exploration of sugar modifications including C5 spirocyclization. Bioorg Med Chem Lett 20:1569-1572.
31. Setter S.M., Iltz J.L., Thams J, and Campbell R.K. (2003) Metformin hydrochloride in the treatment of type 2 diabetes mellitus: A clinical review with a focus on dual therapy. Clin Ther 25:2991-3026. (Pubitemid 38096142)
32. Sha S., Devineni D., Ghosh A., Polidori D., Chien S., Wexler D., Shalayda K., Demarest K, and Rothenberg P. (2011) Canagliflozin, a novel inhibitor of sodium glucose co- Transporter 2, dose dependently reduces calculated renal threshold for glucose excretion and increases urinary glucose excretion in healthy subjects. Diabetes Obes Metab 13:669-672.
33. Stratton I.M., Adler A.I., Neil H.A., Matthews D.R., Manley S.E., Cull C.A., Hadden D., Turner RC, and Holman R.R. (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): Prospective observational study. Br Med J 321:405-412. (Pubitemid 30609442)
34. Wallner E.I., Wada J., Tramonti G., Lin S, and Kanwar Y.S. (2001) Status of glucose transporters in the mammalian kidney and renal development. Ren Fail 23:301-310. (Pubitemid 32692267)
35. Walsky RL and Obach R.S. (2004) Validated assays for human cytochrome P450 activities. Drug Metab Dispos 32:647-660. (Pubitemid 38668158)
36. Wilding J.P., Norwood P, T'joen C, Bastien A, List JF, and Fiedorek FT (2009) A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel insulin- Independent treatment. Diabetes Care 32:1656-1662.
37. +-glucose cotransporters. Am J Physiol Renal Physiol 280:F10-F18.
38. Zhang X., Urbanski M., Patel M., Zeck R.E., Cox G.G., Bian H., Conway B.R., Pat Beavers M., Rybczynski PJ, and Demarest K.T. (2005) Hetero Aryl-O- OGlucosides as novel sodium glucose co- OGlucosides as novel sodium glucose coTransporter 2 inhibitors. Part 1. Bioorg Med Chem Lett 15:5202-5206. (Pubitemid 41463647)
39. Zhang X., Urbanski M., Patel M., Cox G.G., Zeck R.E., Bian H., Conway B.R., Beavers M.P., Rybczynski PJ, and Demarest K.T. (2006) Indole- Glucosides as novel sodium glucose co- Glucosides as novel sodium glucose coTransporter 2 (SGLT2) inhibitors. Part 2. Bioorg Med Chem Lett 16:1696-1701. (Pubitemid 43197548)
40. Zolk O., Solbach T.F., König J, and Fromm M.F. (2009) Structural determinants of inhibitor interaction with the human organic cation transporter OCT2 (SLC22A2). Naunyn- Schmiedebergs Arch Pharmacol 379:337-348.