Influence of temsirolimus on antidiabetic effect of sitagliptin in experimental animal
-
2018-06-14 https://doi.org/10.14419/ijpt.v6i2.11819 -
Influence of Temsirolimus, Antidiabetic Effect of Sitagliptin, Dexamethasone and Drug Interaction. -
Abstract
The present study was carried out to evaluate the drug interaction between an antihyperglycemic agent and anticancerous drug,In healthy and Dexamethasone induced diabetic rats. The blood samples were collected up to 24 h and blood glucose level was estimated. In healthy albino rats Pretreatment with Temsirolimus (6.75 mg/kg for seven days) has significantly altered the onset of hypoglycemia (15.50+1.47 to21.40±.54), p< 0.001 at the 2nd hour significantly enhanced the peak hypoglycemia (29.70+.60 %) before treatment to (44.47+1.21 %) after treatment(p<0.001) at 4th hour (i.e. 18.71±.38 to 20.43±.89, p<0.001 induced by Sitagliptin. Whereas in Dexamethasone treated rats, pretreatment with Temsirolimus (6.75 mg/kg) for 7 days has decreased the onset of hypoglycemia, significantly enhanced the peak hypoglycemia (24.13+.6417%) before treatment to (45.62+2.845 %) after treatment(P<.001) at the 8th hour. This study indicates that therapeutic drug monitoring has been required for therapeutic doses of temsirolimus and antidiabetic drugs when used concomitantly.
HighlightsÂ
1)Â Â Â Â Â Influence of Temsirolimus on hypoglycemic activity of Sitagliptin in healthy rats.
2)Â Â Â Â Â Influence of Temsirolimus on hypoglycemic activity of Sitagliptin in Dexamethasone induced hyperglycemic rats.
3)Â Â Â Â Â To suggest the alteration in the dose and frequency of administration of Oral antidiabetic agents when they are used along with Temsirolimus.
AbbreviationsÂ
P.o.- per os ‘by mouth’, DM-Diabetes mellitus,GOD-Glucose oxidase (GOD), POD- Peroxidase (POD).
Â
-
References
[1] Walker JJ, Brewster DH, Colhoun HM, Fischbacher CM, Lindsay RS & Wild SH (2013). Cause-specific mortality in Scottish patients with colorectal cancer with and without type 2 diabetes. Diabetologia 56, 1531-1541. https://doi.org/10.1007/s00125-013-2917-x.
[2] Tong L, Ahn C, Symanski, E, Lai D & Du XL (2014). Temporal trends in the leading causes of death among a large national cohort of patients with colorectal cancer from 1975 to 2009 in the United States. Annals of epidemiology 24, 411-417. https://doi.org/10.1016/j.annepidem.2014.01.005.
[3] Cos M A & Flórez J (1997). Interacciones de fármacos y sus implicancias clÃnicas. (J. Flórez y col. Eds): Masson SA, Barcelona. En: FarmacologÃa Humana Cap.9, 155-164.
[4] Bapat S P, Myoung S J, Fang S, Liu S,.,Zhang Y, Cheng A, Zhou C, Liang Y, LeBlanc M, Liddle C, Atkins A R, Yu R T, Downes M, Evans R M & Zheng Y (2015). Depletion of fat-resident Treg cells prevents age-associated insulin resistance. Nature 528(7580), 137-41.
[5] Klil-Drori A J, Azoulay L & Pollak M N (2017). Cancer, obesity, diabetes, and antidiabetic drugs: is the fog clearing? Nat Rev Clin Oncol 14(2), 85-99. https://doi.org/10.1038/nrclinonc.2016.120.
[6] Madkhali A A, Fadel Z T, Aljiffry M M & Hassanain M M (2015). Surgical treatment for hepatocellular carcinoma. Saudi J Gastroenterol 21, 11-17. http://www.saudijgastro.com/text.asp?2015/21/1/11/151216. https://doi.org/10.4103/1319-3767.151216.
[7] Tabernero J, Saura C, Roda Perez D,R. Dienstmann R, Rosello S, Prudkin L, Perez-Fidalgo J A, Graña B, Jones C, Musib L, Yan Y, Patel P H, Baselga J, & Cervantes A (2011). First-in-human phase I study evaluating the safety, pharmacokinetics (PK), and intratumor pharmacodynamics (PD) of the novel, oral, ATP-competitive Akt inhibitor GDC-0068. J Clin Oncol 29, 3022-3022. DOI: 10.1200/jco.2011.29.15_suppl.3022 Journal of Clinical Oncology 29, no. 15_suppl (May 20 2011) 3022-3022.
[8] Balkan B, Kwasnik L, Miserendino R , Holst J J & Li X (1999). Inhibition of dipeptidyl peptidase IV with NVP-DPP728 increases plasma GLP-1 (7-36 amide) concentrations and improves oral glucose tolerance in obese Zucker rats. Diabetologia 42(11), 1324-31. https://doi.org/10.1007/s001250051445.
[9] Holst J J & Deacon C F (2004). Glucagon-like peptide 1 and inhibitors of dipeptidyl peptidase IV in the treatment of type 2 diabetes mellitus. Curr Opin Pharmacol 4(6), 589-596. https://doi.org/10.1016/j.coph.2004.08.005.
[10] Matsuo T & Odaka H (1992). Ikeda H. Effect of an intestinal disaccharidase inhibitor (AO-128) on obesity and diabetes. Am J Clin Nutr 55, 314S-317S. https://doi.org/10.1093/ajcn/55.1.314s.
[11] Torre L A, Bray F, Siegel R L, Ferley J, Tieulent J L & Jemal A (2012). Global cancer statistics. CA: Cancer Journal for Clinicians 65, 87–108. https://doi.org/10.3322/caac.21262.
[12] Kasichayanula S, Liu X, Shyu W.C, Zhang W, Pfister M, Griffen S C, Li T, LaCreta P F & Boulton D W (2011). Lack of pharmacokinetic interaction between dapagliflozin, a novel sodium–glucose transporter 2 inhibitor, and metformin, pioglitazone, glimepiride or sitagliptin in healthy subjects. Diabetes, Obesity and Metabolism A Journal of Pharmacology and Therapeutics 13(1), 47-54. https://doi.org/10.1111/j.1463-1326.2010.01314.x.
[13] Bavec A (2014). Insulin, Other Hypoglycaemic Drugs and Glucagon. Side Effects of Drugs Annual 36, 645-657. https://doi.org/10.1016/B978-0-444-63407-8.00042-3.[14] Tornio A, Niemi M, Neuvonen PJ and Backman JT (2012). Drug interactions with oral antidiabetic agents: pharmacokinetic mechanisms and clinical implications. Trends Pharmacol Sci 33(6), 312-22. https://doi.org/10.1016/j.tips.2012.03.001.[15] Patel CG, Kornhauser D, Vachharajani N, Komoroski B, Brenner E, Handschuh del Corral M., Li L and Boulton DW (2011). Saxagliptin, a potent, selective inhibitor of DPP-4, does not alter the pharmacokinetics of three oral antidiabetic drugs (metformin, glyburide or pioglitazone) in healthy subjects. Diabetes Obes Metab 13(7), 604-14. https://doi.org/10.1111/j.1463-1326.2011.01381.x.[16] Levetan C (2007). Oral antidiabetic agents in type 2 diabetes. Curr Med Res Opin, 23(4):945- 52. https://doi.org/10.1185/030079907X178766.
-
Additional Files
-
How to Cite
Jamal, R., K Suresh, D., & S Khalid, M. (2018). Influence of temsirolimus on antidiabetic effect of sitagliptin in experimental animal. International Journal of Pharmacology and Toxicology, 6(2), 24-33. https://doi.org/10.14419/ijpt.v6i2.11819Received date: 2018-04-21
Accepted date: 2018-05-19
Published date: 2018-06-14