BibTex RIS Cite

Eksenatid Kullanımının Toksikolojik Açıdan Değerlendirilmesi

Year 2012, Issue: 2, 159 - 178, 01.06.2012

Abstract

Diabetes mellitus vücudun yeteri kadar insülin üretememesi Tip 1 veya üretilen insüline yeteri kadar yanıt verememesi Tip 2 ile ortaya çıkan ve yüksek kan şekeri ile kendini gösteren bir hastalıktır. İnsülin, pankreasta üretilen ve vücudun glikozu absorplamasını ve enerjiye dönüştürmesini sağlayan bir hormondur ve tip 2 diabette insülin rezistansı söz konusudur. Glukagon benzeri peptit analogları, glukagon benzeri peptit-1 GLP-1 reseptörüne bağlanarak, pankreas β-hücrelerinden insülin salımını artıran ilaçlardır. Endojen GLP-1’nin yarı ömrü çok kısa olduğu için GLP-1 analogları yerine GLP-1 agonistleri uzun yarı ömürleri ile uzun süre insülin salımını sağladıkları için ilaç olarak geliştirilmişlerdir. Eksenatid tip 2 diyabette kullanımı onaylanmış bir GLP reseptör agonisti ve “inkretinmimetik”idir ve oral antidiyabetiklerle tedavi edilemeyen diyabetin tedavisinde önerilmektedir. Etki mekanizması tam olarak bilinmemekle birlikte, pankreatik β-hücrelerinden akut glikoz-bağımlı insülin salımını artırarak açlık ve postprandiyel glisemik kontrolü sağlayan ve gastrik boşalmayı geciktirerek erken tokluk hissini sağlayarak etki gösteren bir ilaçtır. Ayrıca artmış glukagon salımını azaltmaktadır. Ancak ilacın mide boşalma zamanı üzerindeki geciktirici etkisinin bulantı ve kusma gibi ters etkileri beraberinde getirebileceği dikkate alınmalıdır. Diğer taraftan, ilacın neden olabileceği farklı tiplerde pankreatitin hayatı tehdit eden önemli bir hastalık olduğu unutulmamalıdır. İlaç başta hassas popülasyonlar olmak üzere hekim kontrolünde dikkatli bir şekilde kullanılması gerekmektedir. Konu ile ilgili çelişkili hususların kesinleşebilmesi için kapsamlı izleme çalışmaları ve güvenilir geribildirimlerin alınıp değerlendirilmesi gerekmektedir. Bu derlemede eksenatidin toksikolojik profilinden bahsedilecektir ve ilacın farmako/toksiko-kinetiği ve dinamiği, ters etkileri, ilaç etkileşmeleri ve pankreatitle olan ilişkisi değerlendirilecektir.

References

  • Rother, K.I.: Diabetes treatment—bridging the divide. New Eng J Med, 356, 1499 (2007)
  • Tierney, L.M., McPhee S.J., Papadakis M.A., “Current Medical Diagnosis & Treatment”, McPhee, S.J., Papadakis M.A. (Eds.), New York, Lange Medical Books/McGraw-Hill, (2002), sayfa 1203.
  • Carr, D.B., Gabbe, S. : Gestational Diabetes: Detection, Management, and Implications. Clin Diabetes, 16, 4 (1998)
  • Zimmet, P., Alberti, K.G., Shaw, J.: Global and societal implications of the diabetes epidemic. Nature, 414, 782 (2001)
  • Tahrani, A.A., Piya, M.K., Kennedy, A., Barnett, A.H.: Glycaemic control in type 2 dia- betes: targets and new therapies. Pharmacol Ther, 125, 328 (2010)
  • National Library of Medicine - Medical Subject Headings. 2009 MeSH. MeSH Desc- riptor Data. MeSH heading: Incretins. İnternet Adresi: http://www.nlm.nih.gov/cgi/ mesh/2009/MB_cgi. Erişim Tarihi: 19 Eylül 2011.
  • Palalau, A.I., Tahrani, A.A., Piya, M.K., Barnett, A.H.: DPP-4 inhibitors in clinical prac- tice. Postgrad Med, 121, 70 (2009)
  • Baggio, L.L., Drucker, D.J.: Biology of incretins: GLP-1 and GIP. Gastroenterology, 132, 2131 (2007)
  • Kielgast, U., Holst, J.J., Madsbad, S.: Treatment of type 1 diabetic patients with gluca- gon-like peptide-1 (GLP-1) and GLP-1R agonists. Curr Diabetes Rev, 5, 266 (2009)
  • Iltz, J.L., Baker, D.E., Setter, S.M., Campbell, K.R.: Exenatide: an incretin mimetic for the treatment of type 2 diabetes mellitus. Clin Ther, 28, 652 (2006)
  • Chen, Y.E., Drucker, D.J.: Tissue-specific expression of unique mRNAs that encode proglucagon-derived peptides or exendin 4 in the lizard. J Biol Chem, 272, 4108 (1997)
  • Kulasa, K.M., Henry, R.R.: Pharmacotherapy of hyperglycemia. Expert Opin Pharma- cother,10, 2415 (2009)
  • European Medicines Agency. EPARs for Authorised Medicinal Products for Human Use. 2009. İnternet Adresi: http://www.emea.europa.eu/humandocs/Humans/ EPAR/ byetta/byetta.htm. Erişim Tarihi: 19 Eylül 2011.
  • Malone, J., Trautmann, M., Wilhelm, K., Taylor, K., Kendall, D.M.: Exenatide once we- ekly for the treatment of type 2 diabetes. Expert Opin Investig Drugs, 18, 359 (2009)
  • Amylin Pharmaceuticals, Inc. Byetta [package insert]. San Diego, CA: Amylin, 2005. İnternet Adresi: http://pi.lilly.com/us/byetta-pi.pdf. Erişim Tarihi: 19 Eylül 2011.
  • Williams, B., Werner, J., Holst, J. J., Orskov, C., Creutzfeldt, W., Nauck, M.A.: Gastric emptying, glucose responses, and insulin secretion after a liquid test meal: effects of exogenous glucagon-like peptide 1 (GLP-1) (7-36) amide in type 2 (noninsulin depen- dent) diabetic patients. J Clin Endocrinol Metab, 81, 327 (1996)
  • Buse, J.B., Henry, R.R., Han, J., Kim, D.D., Finema,n M.S., Baron, A.D., Exenati- de-113 Clinical Study Group.: Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care, 27, 2628 (2004)
  • Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, Baron AD.: Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care, 2005; 28:1083- 91.
  • Zinman, B., Hoogwerf, B.J., Durán García, S., Milton, D.R., Giaconia, J.M., Kim, D.D., Trautmann, M.E., Brodows, R.G.: The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med, 146, 477 (2007)
  • DeFronzo, R.A., Ratner, R.E., Han, J., Kim, D.D., Fineman, M.S., Baron, A.D.: Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin- treated patients with type 2 diabetes. Diabetes Care, 28, 1092 (2005)
  • Wettergren, A., Schjoldager, B., Mortensen, P.E., Myhre, J., Christiansen, J., Holst, J.J.: Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man. Dig Dis Sci, 38, 665 (1993)
  • Nauck, M.A., Niedereichholz, U., Ettler, R., Holst, J.J., Orskov, C., Ritzel, R., Schmiege,l W.H.: Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotro- pic effects in healthy humans. Am J Physiol, 273, E981 (1997)
  • Tripathy, N.R., Basha, S., Jain, R., Shetty, S., Ramachandran, A.: Exenatide and acute pancreatitis. J Assoc Physicians India, 56, 987 (2008)
  • Pinelli, N.R., Jantz, A., Smith, Z., Abouhassan, A., Ayar, C., Jaber, N.A., Clarke, A.W., Commissaris, R.L, Jaber, L.A.: Effect of Administration Time of Exenatide on Satiety Responses, Blood Glucose, and Adverse Events in Healthy Volunteers. J Clin Pharma- col, 51, 165 (2011)
  • Riddle, M.C., Henry, R.R., Poon, T.H., Zhang, B., Mac, S.M., Holcombe, J.H., Kim, D.D., Maggs, D.G.: Exenatide elicits sustained glycaemic control and progressive reduction of body weight in patients with type 2 diabetes inadequately controlled by sulphonylu- reas with or without metformin. Diabetes Metab Res Rev, 22, 483 (2006)
  • Frey, C.F., Zhou, H., Harvey, D.J., White, R.H.: The incidence and case-fatality rates of acute biliary, alcoholic, and idiopathic pancreatitis in California, 1994-2001. Pancreas, 33, 336 (2006)
  • Noel, R.A., Braun, D.K., Patterson, R.E., Bloomgren, G.L.: Increased risk of acute panc- reatitis and biliary disease observed in patients with type 2 diabetes: a retrospective cohort study. Diabetes Care, 32, 834 (2009)
  • Bain, S.C., Stephens, J.W.: Exenatide and pancreatitis: an update. Expert Opin Drug Saf, 7, 643 (2008)
  • Martínez, J., Johnson, C.D., Sánchez-Payá, J., de Madaria, E., Robles-Díaz, G., Pérez- Mateo, M.: Obesity is a definitive risk factor of severity and mortality in acute pancrea- titis: an updated meta-analysis. Pancreatology, 6, 206 (2006)
  • Dore, D.D., Seeger, J.D., Arnold C.K.: Use of a claims-based active drug safety sur- veillance system to assess the risk of acute pancreatitis with exenatide or sitagliptin compared to metformin or glyburide. Curr Med Res Opin, 25, 1019 (2009)
  • Anderson, S.L., Trujillo, J.M.: Association of pancreatitis with glucagon-like peptide-1 agonist use. Ann Pharmacother, 44, 904 (2010)
  • Kulasa, K.M., Henry, R.R.: Pharmacotherapy of hyperglycemia. Expert Opin Pharma- cother, 10, 2415 (2009)
  • Heine, R.J., Van Gaal, L.F., Johns, D., Mihm, M.J., Widel, M.H., Brodows, R.G.; GWAA Study Group.: Exenatide versus insulin glargine in patients with suboptimally control- led type 2 diabetes: a randomized trial. Ann Intern Med, 143,559 (2005)
  • Barnett, A.H., Trautmann, M., Burger, J.: A comparison of exenatide and insulin glar- gine in patients using a single oral antidiabetic agent. Diabetologia, 49, 474, Abstract 0782 (2006)
  • Faludi, P., Brodows, R., Burger, J., Ivanyi, T., Braun, D.K.: The effect of exenatide re- exposure on safety and efficacy. Peptides, 30, 1771 (2009)
  • Weise, W.J., Sivanandy, M.S., Block, C.A., Comi, R.J.: Exenatide-associated ischemic renal failure. Diabetes Care, 32, e22 (2009)
  • Linnebjerg, H., Kothare, P.A., Park, S., Mace, K., Reddy, S., Mitchell, M., Lins, R.: Effect of renal impairment on the pharmacokinetics of exenatide. Br J Clin Pharmacol, 64, 317 (2007)
  • Robles, G.I., Singh-Franco, D.: A review of exenatide as adjunctive therapy in patients with type 2 diabetes. Drug Des Devel Ther, 3, 219 (2009)
  • Blasé, E., Taylor, K., Gao, H.Y., Wintle, M., Fineman, M.: Pharmacokinetics of an oral drug (acetaminophen) administered at various times in relation to subcutaneous injec- tion of exenatide (exendin-4) in healthy subjects. J Clin Pharmacol, 45, 570 (2005)
  • Kothare, P.A., Soon, D.K., Linnebjerg, H., Park, S., Chan, C., Yeo, A., Lim, M., Mace, K.F., Wise, S.D.: Effect of exenatide on the steady-state pharmacokinetics of digoxin. J Clin Pharmacol, 45, 1032 (2005)
  • Soon, D., Kothare, P.A., Linnebjerg, H., Park, S., Yuen, E., Mace, K.F., Wise, S.D.: Effect of exenatide on the pharmacokinetics and pharmacodynamics of warfarin in healthy Asian men. J Clin Pharmacol, 46, 1179 (2006)
  • Bloomgarden, Z.T.: Diabetes treatment and measures of glycemia. Diabetes Care, 32, e39 (2009)
  • Raman, V.S, Mason, K.J., Rodriguez, L.M., Hassan, K., Yu, X., Bomgaars, L., Heptulla, R.A.: The role of adjunctive exenatide therapy in pediatric type 1 diabetes. Diabetes Care, 33, 1294 (2010)
  • Meneilly, G.S., Greig, N., Tildesley, H., Habener, J.F., Egan, J.M., Elahi, D.: Effects of 3 months of continuous ubcutaneous administration of glucagon-like peptide 1 in elderly patients with type 2 diabetes. Diabetes Care, 26, 2835 (2003)
  • Byetta (Exenatide)—Renal Failure. İnternet Adresi: http://www.fda.gov/Safety/ Med- Watch/ SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm188703.htm. Erişim Tarihi: 19 Eylül 2011.
  • Klonoff, D.C., Buse, J.B., Nielsen, L.L., Guan X., Bowlus, C.L., Holcombe, J.H., Wintle, M.E., Maggs, D.G.: Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin, 24, 275 (2008)
  • Kolterman, O.G., Buse, J.B., Fineman, M.S., Gaines, E., Heintz, S., Bicsak, T.A., Tay- lor, K., Kim, D., Aisporna, M., Wang, Y., Baron AD.: Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab, 2003; 88:3082-9.
  • Gentilella, R., Bianchi, C., Rossi, A., Rotella, C.M.: Exenatide: a review from pharmaco- logy to clinical practice. Diabetes Obes Metab, 11, 544 (2009)
  • Cvetkoviç, R.S., Plosker, G.L.: Exenatide: a review of its use in patients with type 2 diabetes mellitus (as an adjunct to metformin and/or a sulfonylurea). Drugs, 67, 935 (2007)
  • Kolterman, O.G., Kim, D.D., Shen, L., Ruggles, J.A., Nielsen, L.L., Fineman, M.S., Ba- ron, A.D.: Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am J Health Syst Pharm, 62, 173 (2005)
  • Kendall, D., Bhole, D, Guan X.: Exenatide treatment for 82 weeks reduced C-reactive protein HbA1c and body weight in patients with type 2 diabetes mellitus. Diabetologia, 49, 475 (2006)
  • Kapitza, C., Nauck, M., Trautmann, M.: Long-term treatment with exenatide was as- sociated with improved post-prandial glycaemic control and a shift from small to large HDL and LDL particles. Diabetic Med, 23, 532 (2006)
  • Kendall, D., Blonde, L., Mac, S.: Improvements in cardiovascular risk factors ccompa- nied improved glycaemic control and weight reduction in patients with type 2 diabetes treated with exenatide for 3.5y. Diabetes 56, A149 (2007)
  • Heine, R.J., Van Gaal, L.F., Johns, D.: Exenatide achieved equivalent glycaemic control to insulin glargine in metformin and sulphonylurea -treated type 2 diabetics: blood pressure results. JEI, 29, OC28 (2006)
  • Nauck, M.A., Duran, S., Kim, D., Johns, D., Festa, A., Trautman, M.: Effects of exena- tide compared with twice-daily biphasic insulin aspart in patients with type 2 diabetes using metformin and a sulphonylurea. Diabetologia, 49, 3 (2006)
  • Byetta. Precautions page. İnternet Adresi: http://www.rxlist.com/byetta-drug.htm. Erişim Tarihi: 19 Eylül 2011.
  • Feng, Y.H., Velazquez-Torre, G., Gully, C., Chen, J., Lee, M.H., Yeung, S.C.: The impact of type 2 diabetes and antidiabetic drugs on cancer cell growth. J Cell Mol Med, 15, 825 (2011)
  • Bjerre Knudsen, L., Madsen, L.W., Andersen, S., Almholt, K., de Boer, A.S., Drucker, D.J., Gotfredsen, C., Egerod, F.L., Hegelund, A.C., Jacobsen, H., Jacobsen, S.D., Mo- ses, A.C., Mİlck,, A.M., Nielsen, H.S., Nowak, J., Solberg, H., Thi, T.D., Zdravkovic, M.: Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology, 151, 1473 (2010)
  • Blonde, R.: Assessing the Potential Association Between GLP-1-Based Therapies and Thyroid Tumors. MedSpace CME Online. İnternet Adresi: http://cme.medscape.com/ viewarticle/728112_transcript. Erişim Tarihi: 19 Eylül 2011.
  • Fineman, M.S., Bicsak, T.A., Shen, L.Z., Taylor, K., Gaines, E., Varns, A., Kim, D., Baron, A.D.: Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes. Diabetes Care 26, 2370 (2003)
  • International Expert Committee.: International expert committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 32, 1327 (2009)
  • Blonde, L., Klein, E.J., Han, J., Zhang, B., Mac S.M., Poon, T.H., Taylor, K.L., Traut- mann, M.E., Kim, D.D., Kendall, D.M.: Interim analysis of the effects of exenatide tre- atment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab, 8, 436 (2006)
  • Mitri, J., Hamdy, O.: Diabetes medications and body weight. Expert Opin Drug Saf, 8, 573 (2009)
  • Barnett, A.H., Burger, J., Johns, D., Brodows, R., Kendall, D.M., Roberts, A., Traut- mann, M.E.: Tolerability and efficacy of exenatide and titrated insulin glargine in adult patients with type 2 diabetes previously uncontrolled with metformin or a sulfonylu- rea: a multinational, randomized, open-label, two-period, crossover noninferiority trial. Clin Ther, 29, 2333 (2007)
  • Gentilella, R., Bianchi, C., Rossi, A., Rotella, C.M.: Exenatide: a review from pharmaco- logy to clinical practice. Diabetes Obes Metab, 11, 544 (2009)

Toxicological Evaluation of Exenatide Usage

Year 2012, Issue: 2, 159 - 178, 01.06.2012

Abstract

Diabetes mellitus is a disease in which a person has a high blood glucose level as a result of the body’s either not producing enough insulin type 1 , or because body cells do not properly respond or are resistant to the insulin that is produced type 2 . Insulin is synthesized in pancreas; it is responsible for the absorption and conversion of glucose to energy. Glucagon-like peptide analogues are drugs that bind to glucagon- like peptide-1 GLP-1 receptor and enhance insulin secretion from pancreatic β-cells. As the half-life of GLP-1 is very short, instead of GLP-1 analogues, GLP-1 agonists with long half-lives are developed to provide longer duration of insulin secretion. Exenatide is an approved GLP-1 agonist and “incretinmimetic” used in type 2 diabetes and is suggested in diabetes that cannot be treated with oral antidiabetics. Though its mode of action is not clear, it is a drug that controls fasting and postprandial glycemia by increasing glucose-dependent insulin secretion from pancreatic β-cells and enables satiety in shorter period. However, the drug prolongs the gastric emptying time and this brings the side effects nausea and vomiting in turn. On the other hand, it should not be forgotten that the drug causes different types of pancreatitis which is a serious lifethreatening disease. The drug must be used with caution by prescription. Comprehensive surveillance studies and reliable feedbacks are needed to evaluate the clarification of contradictory issues in the usage of this particular drug. This review will focus on the toxicological profile of exenatide: pharmaco/toxico-kinetics and dynamics, safety/efficacy, adverse reactions, drug interactions and its relationship with pancreatitis.

References

  • Rother, K.I.: Diabetes treatment—bridging the divide. New Eng J Med, 356, 1499 (2007)
  • Tierney, L.M., McPhee S.J., Papadakis M.A., “Current Medical Diagnosis & Treatment”, McPhee, S.J., Papadakis M.A. (Eds.), New York, Lange Medical Books/McGraw-Hill, (2002), sayfa 1203.
  • Carr, D.B., Gabbe, S. : Gestational Diabetes: Detection, Management, and Implications. Clin Diabetes, 16, 4 (1998)
  • Zimmet, P., Alberti, K.G., Shaw, J.: Global and societal implications of the diabetes epidemic. Nature, 414, 782 (2001)
  • Tahrani, A.A., Piya, M.K., Kennedy, A., Barnett, A.H.: Glycaemic control in type 2 dia- betes: targets and new therapies. Pharmacol Ther, 125, 328 (2010)
  • National Library of Medicine - Medical Subject Headings. 2009 MeSH. MeSH Desc- riptor Data. MeSH heading: Incretins. İnternet Adresi: http://www.nlm.nih.gov/cgi/ mesh/2009/MB_cgi. Erişim Tarihi: 19 Eylül 2011.
  • Palalau, A.I., Tahrani, A.A., Piya, M.K., Barnett, A.H.: DPP-4 inhibitors in clinical prac- tice. Postgrad Med, 121, 70 (2009)
  • Baggio, L.L., Drucker, D.J.: Biology of incretins: GLP-1 and GIP. Gastroenterology, 132, 2131 (2007)
  • Kielgast, U., Holst, J.J., Madsbad, S.: Treatment of type 1 diabetic patients with gluca- gon-like peptide-1 (GLP-1) and GLP-1R agonists. Curr Diabetes Rev, 5, 266 (2009)
  • Iltz, J.L., Baker, D.E., Setter, S.M., Campbell, K.R.: Exenatide: an incretin mimetic for the treatment of type 2 diabetes mellitus. Clin Ther, 28, 652 (2006)
  • Chen, Y.E., Drucker, D.J.: Tissue-specific expression of unique mRNAs that encode proglucagon-derived peptides or exendin 4 in the lizard. J Biol Chem, 272, 4108 (1997)
  • Kulasa, K.M., Henry, R.R.: Pharmacotherapy of hyperglycemia. Expert Opin Pharma- cother,10, 2415 (2009)
  • European Medicines Agency. EPARs for Authorised Medicinal Products for Human Use. 2009. İnternet Adresi: http://www.emea.europa.eu/humandocs/Humans/ EPAR/ byetta/byetta.htm. Erişim Tarihi: 19 Eylül 2011.
  • Malone, J., Trautmann, M., Wilhelm, K., Taylor, K., Kendall, D.M.: Exenatide once we- ekly for the treatment of type 2 diabetes. Expert Opin Investig Drugs, 18, 359 (2009)
  • Amylin Pharmaceuticals, Inc. Byetta [package insert]. San Diego, CA: Amylin, 2005. İnternet Adresi: http://pi.lilly.com/us/byetta-pi.pdf. Erişim Tarihi: 19 Eylül 2011.
  • Williams, B., Werner, J., Holst, J. J., Orskov, C., Creutzfeldt, W., Nauck, M.A.: Gastric emptying, glucose responses, and insulin secretion after a liquid test meal: effects of exogenous glucagon-like peptide 1 (GLP-1) (7-36) amide in type 2 (noninsulin depen- dent) diabetic patients. J Clin Endocrinol Metab, 81, 327 (1996)
  • Buse, J.B., Henry, R.R., Han, J., Kim, D.D., Finema,n M.S., Baron, A.D., Exenati- de-113 Clinical Study Group.: Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care, 27, 2628 (2004)
  • Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, Baron AD.: Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care, 2005; 28:1083- 91.
  • Zinman, B., Hoogwerf, B.J., Durán García, S., Milton, D.R., Giaconia, J.M., Kim, D.D., Trautmann, M.E., Brodows, R.G.: The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med, 146, 477 (2007)
  • DeFronzo, R.A., Ratner, R.E., Han, J., Kim, D.D., Fineman, M.S., Baron, A.D.: Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin- treated patients with type 2 diabetes. Diabetes Care, 28, 1092 (2005)
  • Wettergren, A., Schjoldager, B., Mortensen, P.E., Myhre, J., Christiansen, J., Holst, J.J.: Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man. Dig Dis Sci, 38, 665 (1993)
  • Nauck, M.A., Niedereichholz, U., Ettler, R., Holst, J.J., Orskov, C., Ritzel, R., Schmiege,l W.H.: Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotro- pic effects in healthy humans. Am J Physiol, 273, E981 (1997)
  • Tripathy, N.R., Basha, S., Jain, R., Shetty, S., Ramachandran, A.: Exenatide and acute pancreatitis. J Assoc Physicians India, 56, 987 (2008)
  • Pinelli, N.R., Jantz, A., Smith, Z., Abouhassan, A., Ayar, C., Jaber, N.A., Clarke, A.W., Commissaris, R.L, Jaber, L.A.: Effect of Administration Time of Exenatide on Satiety Responses, Blood Glucose, and Adverse Events in Healthy Volunteers. J Clin Pharma- col, 51, 165 (2011)
  • Riddle, M.C., Henry, R.R., Poon, T.H., Zhang, B., Mac, S.M., Holcombe, J.H., Kim, D.D., Maggs, D.G.: Exenatide elicits sustained glycaemic control and progressive reduction of body weight in patients with type 2 diabetes inadequately controlled by sulphonylu- reas with or without metformin. Diabetes Metab Res Rev, 22, 483 (2006)
  • Frey, C.F., Zhou, H., Harvey, D.J., White, R.H.: The incidence and case-fatality rates of acute biliary, alcoholic, and idiopathic pancreatitis in California, 1994-2001. Pancreas, 33, 336 (2006)
  • Noel, R.A., Braun, D.K., Patterson, R.E., Bloomgren, G.L.: Increased risk of acute panc- reatitis and biliary disease observed in patients with type 2 diabetes: a retrospective cohort study. Diabetes Care, 32, 834 (2009)
  • Bain, S.C., Stephens, J.W.: Exenatide and pancreatitis: an update. Expert Opin Drug Saf, 7, 643 (2008)
  • Martínez, J., Johnson, C.D., Sánchez-Payá, J., de Madaria, E., Robles-Díaz, G., Pérez- Mateo, M.: Obesity is a definitive risk factor of severity and mortality in acute pancrea- titis: an updated meta-analysis. Pancreatology, 6, 206 (2006)
  • Dore, D.D., Seeger, J.D., Arnold C.K.: Use of a claims-based active drug safety sur- veillance system to assess the risk of acute pancreatitis with exenatide or sitagliptin compared to metformin or glyburide. Curr Med Res Opin, 25, 1019 (2009)
  • Anderson, S.L., Trujillo, J.M.: Association of pancreatitis with glucagon-like peptide-1 agonist use. Ann Pharmacother, 44, 904 (2010)
  • Kulasa, K.M., Henry, R.R.: Pharmacotherapy of hyperglycemia. Expert Opin Pharma- cother, 10, 2415 (2009)
  • Heine, R.J., Van Gaal, L.F., Johns, D., Mihm, M.J., Widel, M.H., Brodows, R.G.; GWAA Study Group.: Exenatide versus insulin glargine in patients with suboptimally control- led type 2 diabetes: a randomized trial. Ann Intern Med, 143,559 (2005)
  • Barnett, A.H., Trautmann, M., Burger, J.: A comparison of exenatide and insulin glar- gine in patients using a single oral antidiabetic agent. Diabetologia, 49, 474, Abstract 0782 (2006)
  • Faludi, P., Brodows, R., Burger, J., Ivanyi, T., Braun, D.K.: The effect of exenatide re- exposure on safety and efficacy. Peptides, 30, 1771 (2009)
  • Weise, W.J., Sivanandy, M.S., Block, C.A., Comi, R.J.: Exenatide-associated ischemic renal failure. Diabetes Care, 32, e22 (2009)
  • Linnebjerg, H., Kothare, P.A., Park, S., Mace, K., Reddy, S., Mitchell, M., Lins, R.: Effect of renal impairment on the pharmacokinetics of exenatide. Br J Clin Pharmacol, 64, 317 (2007)
  • Robles, G.I., Singh-Franco, D.: A review of exenatide as adjunctive therapy in patients with type 2 diabetes. Drug Des Devel Ther, 3, 219 (2009)
  • Blasé, E., Taylor, K., Gao, H.Y., Wintle, M., Fineman, M.: Pharmacokinetics of an oral drug (acetaminophen) administered at various times in relation to subcutaneous injec- tion of exenatide (exendin-4) in healthy subjects. J Clin Pharmacol, 45, 570 (2005)
  • Kothare, P.A., Soon, D.K., Linnebjerg, H., Park, S., Chan, C., Yeo, A., Lim, M., Mace, K.F., Wise, S.D.: Effect of exenatide on the steady-state pharmacokinetics of digoxin. J Clin Pharmacol, 45, 1032 (2005)
  • Soon, D., Kothare, P.A., Linnebjerg, H., Park, S., Yuen, E., Mace, K.F., Wise, S.D.: Effect of exenatide on the pharmacokinetics and pharmacodynamics of warfarin in healthy Asian men. J Clin Pharmacol, 46, 1179 (2006)
  • Bloomgarden, Z.T.: Diabetes treatment and measures of glycemia. Diabetes Care, 32, e39 (2009)
  • Raman, V.S, Mason, K.J., Rodriguez, L.M., Hassan, K., Yu, X., Bomgaars, L., Heptulla, R.A.: The role of adjunctive exenatide therapy in pediatric type 1 diabetes. Diabetes Care, 33, 1294 (2010)
  • Meneilly, G.S., Greig, N., Tildesley, H., Habener, J.F., Egan, J.M., Elahi, D.: Effects of 3 months of continuous ubcutaneous administration of glucagon-like peptide 1 in elderly patients with type 2 diabetes. Diabetes Care, 26, 2835 (2003)
  • Byetta (Exenatide)—Renal Failure. İnternet Adresi: http://www.fda.gov/Safety/ Med- Watch/ SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm188703.htm. Erişim Tarihi: 19 Eylül 2011.
  • Klonoff, D.C., Buse, J.B., Nielsen, L.L., Guan X., Bowlus, C.L., Holcombe, J.H., Wintle, M.E., Maggs, D.G.: Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin, 24, 275 (2008)
  • Kolterman, O.G., Buse, J.B., Fineman, M.S., Gaines, E., Heintz, S., Bicsak, T.A., Tay- lor, K., Kim, D., Aisporna, M., Wang, Y., Baron AD.: Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab, 2003; 88:3082-9.
  • Gentilella, R., Bianchi, C., Rossi, A., Rotella, C.M.: Exenatide: a review from pharmaco- logy to clinical practice. Diabetes Obes Metab, 11, 544 (2009)
  • Cvetkoviç, R.S., Plosker, G.L.: Exenatide: a review of its use in patients with type 2 diabetes mellitus (as an adjunct to metformin and/or a sulfonylurea). Drugs, 67, 935 (2007)
  • Kolterman, O.G., Kim, D.D., Shen, L., Ruggles, J.A., Nielsen, L.L., Fineman, M.S., Ba- ron, A.D.: Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am J Health Syst Pharm, 62, 173 (2005)
  • Kendall, D., Bhole, D, Guan X.: Exenatide treatment for 82 weeks reduced C-reactive protein HbA1c and body weight in patients with type 2 diabetes mellitus. Diabetologia, 49, 475 (2006)
  • Kapitza, C., Nauck, M., Trautmann, M.: Long-term treatment with exenatide was as- sociated with improved post-prandial glycaemic control and a shift from small to large HDL and LDL particles. Diabetic Med, 23, 532 (2006)
  • Kendall, D., Blonde, L., Mac, S.: Improvements in cardiovascular risk factors ccompa- nied improved glycaemic control and weight reduction in patients with type 2 diabetes treated with exenatide for 3.5y. Diabetes 56, A149 (2007)
  • Heine, R.J., Van Gaal, L.F., Johns, D.: Exenatide achieved equivalent glycaemic control to insulin glargine in metformin and sulphonylurea -treated type 2 diabetics: blood pressure results. JEI, 29, OC28 (2006)
  • Nauck, M.A., Duran, S., Kim, D., Johns, D., Festa, A., Trautman, M.: Effects of exena- tide compared with twice-daily biphasic insulin aspart in patients with type 2 diabetes using metformin and a sulphonylurea. Diabetologia, 49, 3 (2006)
  • Byetta. Precautions page. İnternet Adresi: http://www.rxlist.com/byetta-drug.htm. Erişim Tarihi: 19 Eylül 2011.
  • Feng, Y.H., Velazquez-Torre, G., Gully, C., Chen, J., Lee, M.H., Yeung, S.C.: The impact of type 2 diabetes and antidiabetic drugs on cancer cell growth. J Cell Mol Med, 15, 825 (2011)
  • Bjerre Knudsen, L., Madsen, L.W., Andersen, S., Almholt, K., de Boer, A.S., Drucker, D.J., Gotfredsen, C., Egerod, F.L., Hegelund, A.C., Jacobsen, H., Jacobsen, S.D., Mo- ses, A.C., Mİlck,, A.M., Nielsen, H.S., Nowak, J., Solberg, H., Thi, T.D., Zdravkovic, M.: Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology, 151, 1473 (2010)
  • Blonde, R.: Assessing the Potential Association Between GLP-1-Based Therapies and Thyroid Tumors. MedSpace CME Online. İnternet Adresi: http://cme.medscape.com/ viewarticle/728112_transcript. Erişim Tarihi: 19 Eylül 2011.
  • Fineman, M.S., Bicsak, T.A., Shen, L.Z., Taylor, K., Gaines, E., Varns, A., Kim, D., Baron, A.D.: Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes. Diabetes Care 26, 2370 (2003)
  • International Expert Committee.: International expert committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 32, 1327 (2009)
  • Blonde, L., Klein, E.J., Han, J., Zhang, B., Mac S.M., Poon, T.H., Taylor, K.L., Traut- mann, M.E., Kim, D.D., Kendall, D.M.: Interim analysis of the effects of exenatide tre- atment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab, 8, 436 (2006)
  • Mitri, J., Hamdy, O.: Diabetes medications and body weight. Expert Opin Drug Saf, 8, 573 (2009)
  • Barnett, A.H., Burger, J., Johns, D., Brodows, R., Kendall, D.M., Roberts, A., Traut- mann, M.E.: Tolerability and efficacy of exenatide and titrated insulin glargine in adult patients with type 2 diabetes previously uncontrolled with metformin or a sulfonylu- rea: a multinational, randomized, open-label, two-period, crossover noninferiority trial. Clin Ther, 29, 2333 (2007)
  • Gentilella, R., Bianchi, C., Rossi, A., Rotella, C.M.: Exenatide: a review from pharmaco- logy to clinical practice. Diabetes Obes Metab, 11, 544 (2009)
There are 65 citations in total.

Details

Primary Language Turkish
Journal Section Research Article
Authors

Pınar Erkekoğlu This is me

Belma Koçer Gümüşel This is me

Gönül Şahin

Publication Date June 1, 2012
Published in Issue Year 2012 Issue: 2

Cite

Vancouver Erkekoğlu P, Gümüşel BK, Şahin G. Eksenatid Kullanımının Toksikolojik Açıdan Değerlendirilmesi. HUJPHARM. 2012(2):159-78.