Influence of renal or hepatic impairment on the pharmacokinetics of saxagliptin

Clinical Pharmacokinetics

Volumn 50, Issue 4, 2011, Pages 253-265

  Boulton, David W ^a   Li, Li ^a   Frevert, Ernst U ^a   Tang, Angela ^a   Castaneda, Lorna ^a   Vachharajani, Nimish N ^a   Kornhauser, David M ^a   Patel, Chirag G ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

Antihyperglycaemics, pharmacokinetics; Diabetes mellitus; Dipeptides, pharmacokinetics; Haemodialysis; Liver dysfunction; Renal impairment; Research and development; Saxagliptin, pharmacokinetics; Type 2 diabetes mellitus

Indexed keywords

5 HYDROXY SAXAGLIPTIN; ANTILIPEMIC AGENT; CREATININE; CYTOCHROME P450 3A INHIBITOR; CYTOCHROME P450 INHIBITOR; DIPEPTIDYL PEPTIDASE IV INHIBITOR; IOHEXOL; NIFEDIPINE; SAXAGLIPTIN; SPIRONOLACTONE; UNCLASSIFIED DRUG;

ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; BODY WEIGHT; CONTROLLED STUDY; CREATININE CLEARANCE; DIARRHEA; DISEASE SEVERITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXPOSURE; DRUG FATALITY; DRUG HALF LIFE; DRUG MEGADOSE; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; DRUG URINE LEVEL; FEMALE; HEMODIALYSIS; HUMAN; HYPERLIPIDEMIA; HYPERSPLENISM; KIDNEY DYSFUNCTION; KIDNEY FAILURE; KIDNEY FUNCTION; LIVER DISEASE; LIVER DYSFUNCTION; LIVER FUNCTION TEST; MAJOR CLINICAL STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; METABOLITE; MULTICENTER STUDY; MYALGIA; OPEN STUDY; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; SIDE EFFECT; SINGLE DRUG DOSE; SMOKING HABIT; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADAMANTANE; ADULT; AGED; DIABETES MELLITUS, TYPE 2; DIALYSIS SOLUTIONS; DIPEPTIDES; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; FEMALE; HALF-LIFE; HEPATIC INSUFFICIENCY; HUMANS; HYPOGLYCEMIC AGENTS; KIDNEY FAILURE, CHRONIC; MALE; METABOLIC CLEARANCE RATE; MIDDLE AGED; RENAL DIALYSIS; RENAL INSUFFICIENCY; SEVERITY OF ILLNESS INDEX;

EID: 79952088990     PISSN: 03125963     EISSN: 11791926     Source Type: Journal    
DOI: 10.2165/11584350-000000000-00000     Document Type: Article

References (25)

1. WHO. Diabetes [fact sheet no. 312; online]. Available from URL: http://www.who.int/mediacentre/factsheets/fs312/en/ [Accessed 2010 Dec 1]
2. US Renal Data System. Annual data report: 2007. Atlas of chronic kidney disease and end-stage renal disease in the United States [online]. Available from URL: www.usrds.org/adr-2007.htm [Accessed 2010 Dec 1]
3. Bash LD, Selvin E, Steffes M, et al. Poor glycemic control in diabetes and the risk of incident chronic kidney disease even in the absence of albuminuria and retinopathy. Arch Intern Med 2008; 168: 2440-7
4. Poonawala A, Nair SP, Thuluvath PJ. Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: a case-control study. Hepatology 2000; 32 (4 Pt 1): 689-92
5. El-Serag HB, Tran T, Everharts JE. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology 2004; 126: 460-8 6.
6. Glucophage® (metformin hydrochloride): US prescribing information [online]. Available from URL: http://packageinserts.bms.com/pi/pi-glucophage.pdf [Accessed 2010 Dec 1]
7. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA 2002; 287: 360-72 (Pubitemid 34256388)
8. Odegard PS, Setter SM, Neumiller JJ. Considerations for the pharmacological treatment of diabetes in older adults. Diabetes Spectrum 2007; 20: 239-46
9. Rodighiero V. Effects of liver disease on pharmacokinetics: an update. Clin Pharmacokinet 1999; 37: 399-431
10. Tahrani AA, Piya MK, Barnett AH. Saxagliptin: a new DPP-4 inhibitor for the treatment of type 2 diabetes mellitus. Adv Ther 2009; 26: 249-62
11. Rosenstock J, Sankoh S, List JF. Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diabetes Obes Metab 2008; 10: 376-86 (Pubitemid 351524285)
12. DeFronzo RA, Hissa M, Garber AJ, et al. The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes on metformin alone. Diabetes Care 2009; 32: 1649-55
13. Chacra AR, Tan GH, Apanovitch A, et al. Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial. Int J Clin Pract 2009; 63: 1395-406
14. Jadzinsky M, Pfützner A, Paz-Pacheco E, et al. Saxagliptin given in combination with metformin as initial therapy improves glycemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial. Diabetes Obes Metab 2009; 11 (6): 611-22
15. Hollander P, Li J, Allen E, et al. Saxagliptin added to a thiazolidinedione improves glycemic control in patients with type 2 diabetes and inadequate control on thiazolidinedione alone. J Clin Endocrinol Metab 2009; 94 (12): 4810-9
16. Onglyza™ (saxagliptin): US prescribing information [online]. Available from URL: http://packageinserts.bms.com/pi/pi-onglyza.pdf [Accessed 2010Dec 1]
17. DeFronzo R, Hissa MN, Garber AJ, et al. Once daily saxagliptin added to metformin provides sustained glycemic control and is well tolerated over 102 weeks in patients with T2D [abstract]. Diabetes 2009; 58 Suppl. 1: A147
18. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16 (1): 31-41
19. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994
20. Boulton D, Goyal A, Li L, et al. The effects of age and gender on the single-dose pharmacokinetics and safety of saxagliptin in healthy subjects [abstract]. Diabetes 2008; 57 Suppl. 1: A164
21. Bristol-Myers Squibb/AstraZeneca. Saxagliptin clinical pharmacology summary. Princeton (NJ): Bristol-Myers Squibb, and Wilmington (DE): AstraZeneca, 2008 (Data on file)
22. Testa R, Caglieris S, Risso D, et al. Monoethylglycinexylidide formation measurement as a hepatic function test to assess severity of chronic liver disease. Am J Gastroenterol 1997; 92: 2268-73
23. Uderman H. Placebo-controlled, ascending single-dose study to evaluate the safety, pharmacokinetics, and pharmacodynamics of BMS-47718 in healthy subjects. Lawrenceville (NJ): Bristol-Myers Squibb, 2005 (Data on file)
24. European Medicines Agency. Onglyza (saxagliptin): summary of product characteristics [online].Available fromURL: http://www.ema.europa.eu/docs/en-GB/ document-library/EPAR---Product-Information/human/001039/WC500044316.pdf [Accessed 2010 Dec 1]
25. Nowicki M, Rychlik I, Haller H, et al. Saxagliptin improves glycemic control and is well tolerated in patients with type 2 diabetes mellitus (T2DM)and renal impairment compared with placebo [abstract].Diabetes 2010; 59 Suppl. 1:A149