ساكساغلبتين - تاريخ المراجعة

كنان الطرح في 16:16، 21 أبريل 2013

2013-04-21T16:16:30Z

@@ سطر 139: / سطر 139: @@
   -->
 ==المصادر==
 {{reflist}}

كنان الطرح: /* روابط خارجية */

2013-04-19T19:47:50Z

روابط خارجية

→ مراجعة أقدم		مراجعة 19:47، 19 أبريل 2013
سطر 147:		سطر 147:
	*[http://www.forbes.com/2004/01/26/cx_mh_rl_diabetestearsheet_5.html The race to get DPP-4 inhibitors to market] - Forbes.com		*[http://www.forbes.com/2004/01/26/cx_mh_rl_diabetestearsheet_5.html The race to get DPP-4 inhibitors to market] - Forbes.com
	*{{cite web\|url=http://www.medpagetoday.com/Washington-Watch/Washington-Watch/13555\|title=Saxagliptin First Diabetes Drug to Pass FDA Cardiovascular Safety Review\|last=Walker\|first=Emily P.\|work=}}		*{{cite web\|url=http://www.medpagetoday.com/Washington-Watch/Washington-Watch/13555\|title=Saxagliptin First Diabetes Drug to Pass FDA Cardiovascular Safety Review\|last=Walker\|first=Emily P.\|work=}}

	{{بذرة}}		{{بذرة}}
	{{Oral hypoglycemics}}		{{Oral hypoglycemics}}
	[[تصنيف:أدوية]]		[[تصنيف:أدوية]]
	[[تصنيف:موسوعة الأدوية]]		[[تصنيف:موسوعة الأدوية]]
	[[~~Category~~:~~Dipeptidyl peptidase-4 inhibitors]]~~		[[تصنيف:خافضات سكر الدم]]
	~~[[Category:Nitriles]]~~
	~~[[Category:Bristol-Myers Squibb]]~~
	~~[[Category:Adamantanes]]~~
	~~[[Category:Alcohols]]~~
	~~[[Category:Amides]]~~
	~~[[Category:Nitrogen heterocycles~~]]

إدارة الموسوعة: متابعة ترجمة

2013-03-28T09:28:08Z

متابعة ترجمة

→ مراجعة أقدم		مراجعة 09:28، 28 مارس 2013
سطر 50:		سطر 50:
	\| StdInChIKey = QGJUIPDUBHWZPV-SGTAVMJGSA-N		\| StdInChIKey = QGJUIPDUBHWZPV-SGTAVMJGSA-N
	}}		}}
	الساكساغلبتين {{إنج\|Saxagliptin}} ([[International Nonproprietary Name\|rINN]]) سمي سابقاً '''BMS-477118''' وهو دواء فموي لمرض السكري من مثبطات DPP-4		الساكساغلبتين {{إنج\|Saxagliptin}} ([[International Nonproprietary Name\|rINN]]) سمي سابقاً '''BMS-477118''' وهو دواء فموي لمرض السكري من مثبطات DPP-4
	~~<!--~~
	'''Saxagliptin''' ([[International Nonproprietary Name\|rINN]]), previously identified as '''BMS-477118''', is a new oral hypoglycemic ([[anti-diabetic drug]]) of the new [[DPP-4 inhibitors\|dipeptidyl peptidase-4 (DPP-4) inhibitor]] class of drugs.<ref name="ahren">{{cite journal \| author = Augeri D ''et al.''		<ref name="ahren">{{cite journal \| author = Augeri D ''et al.''
	\| title = Discovery and preclinical profile of Saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes		\| title = Discovery and preclinical profile of Saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
	\| journal = [[Journal of Medicinal Chemistry]] \| volume = 48 \| issue = 15 \| pages = 5025–5037 \| year = 2005		\| journal = [[Journal of Medicinal Chemistry]] \| volume = 48 \| issue = 15 \| pages = 5025–5037 \| year = 2005
	\| pmid = 16033281\| doi = 10.1021/jm050261p}}</ref> ~~Early development was solely by [[Bristol-Myers Squibb]]; in~~ 2007 [[AstraZeneca]] joined with Bristol-Myers Squibb to co-develop the final compound and collaborate on the marketing of the drug. A New Drug Application for saxagliptin in the treatment of type 2 diabetes was submitted to the FDA ~~in June 2008. It was based on a drug development program with 8 randomized trials: 1 phase 2 dose-ranging (2.5–100 mg/d) study;~~ 6 ~~phase 3, 24~~-week controlled trials with additional controlled follow-up from 12 to 42 months, double-blinded throughout; and one 12-week mechanism-of-action trial with a 2-year follow-up period.<ref name="Postgraduate Medicine 2010">{{cite journal \| author=Robert Frederich, MD, PhD et al. \| title=A Systematic Assessment of Cardiovascular Outcomes in the Saxagliptin Drug Development Program for Type 2 Diabetes \| journal=Postgraduate Medicine. \| month=May \| year=2010 \| pages=16–27 \| volume=122 \| issue=3 \| url=http://www.postgradmed.com/index.php?article=2138#none \| doi=10.3810/pgm.2010.05.2138 \| pmid=20463410}}</ref> In June 2008~~, it was announced that '''Onglyza''' would be the trade name under which saxagliptin will be marketed.<ref name="Bloomberg">{{cite news\| url=http~~:~~//www.bloomberg.com/apps/news?pid=20601103&sid=amRAcE.Jql6g&refer=news \| work=Bloomberg \| title=Bristol, Takeda Drugs Offer Alternatives to Januvia (Update2) \| date=2008-06-07}}</ref>~~		\| pmid = 16033281\| doi = 10.1021/jm050261p}}</ref>
			تم تطويره بداية من شكرة بريستول مايرز سكويب ثم في 2007 اشتركت أسترازنيكا في التططوير إلى المنتج النهائي وشاركت في تسويق الدواء، وتم طرح ترخيص تسويق تطبيق دواء جديد NDA لإدارة الغذاء والدواء الأمريكية FDA كدواء لعلاج السكري من النمط الثاني في 6-2008 بناء على ثمانية تجارب بنمط العشوائية:

	~~The FDA approved Saxagliptin~~ with ~~brand~~ name Onglyza ~~on July~~ 31, 2009.<ref>{{cite news		* : 1 phase 2 dose-ranging (2.5–100 mg/d) study;
			* 6 phase 3, 24-week controlled trials with additional controlled follow-up from 12 to 42 months, double-blinded throughout;
			* and one 12-week mechanism-of-action trial with a 2-year follow-up period
			.<ref name="Postgraduate Medicine 2010">{{cite journal \| author=Robert Frederich, MD, PhD et al. \| title=A Systematic Assessment of Cardiovascular Outcomes in the Saxagliptin Drug Development Program for Type 2 Diabetes \| journal=Postgraduate Medicine. \| month=May \| year=2010 \| pages=16–27 \| volume=122 \| issue=3 \| url=http://www.postgradmed.com/index.php?article=2138#none \| doi=10.3810/pgm.2010.05.2138 \| pmid=20463410}}</ref>
			في 6-2008 تم الإعلان عن اسم تجاري للدواء '''Onglyza''' .<ref name="Bloomberg">{{cite news\| url=http://www.bloomberg.com/apps/news?pid=20601103&sid=amRAcE.Jql6g&refer=news \| work=Bloomberg \| title=Bristol, Takeda Drugs Offer Alternatives to Januvia (Update2) \| date=2008-06-07}}</ref> وافقت إدارة الغذاء والدواء الأمكريكية في 31-7-2009 .<ref>{{cite news
	\| author = Telegram \| title = FDA approves diabetes drug from two area manufacturers		\| author = Telegram \| title = FDA approves diabetes drug from two area manufacturers
	\| url = http://www.telegram.com/article/20090802/NEWS/908020328/1002		\| url = http://www.telegram.com/article/20090802/NEWS/908020328/1002
	\| publisher = Worcester Telegram & Gazette Corp. \| date = 2 August 2009 \| accessdate = 2009-08-02		\| publisher = Worcester Telegram & Gazette Corp. \| date = 2 August 2009 \| accessdate = 2009-08-02
	}}</ref>		}}</ref> ويعتقد أن دور أنزيم Dipeptidyl peptidase-4 في تنظيم سكر الدم هو عبر تدرك glucose-dependent insulinotropic peptide GIP<ref name="mentlein">{{cite journal

	Dipeptidyl peptidase-4~~'s role in [[blood glucose]] regulation is thought to be through degradation of [[~~glucose-dependent insulinotropic peptide\|GIP]]<ref name="mentlein">{{cite journal
	\| last = Mentlein \| first = R \| authorlink = \| coauthors = Gallwitz, B; Schmidt, WE		\| last = Mentlein \| first = R \| authorlink = \| coauthors = Gallwitz, B; Schmidt, WE
	\| date = 15 June 1993 \| accessdate = 2007-01-11		\| date = 15 June 1993 \| accessdate = 2007-01-11
سطر 69:		سطر 72:
	\| journal = [[European Journal of Biochemistry]] \| volume = 214 \| issue = 3 \| pages = 829–835		\| journal = [[European Journal of Biochemistry]] \| volume = 214 \| issue = 3 \| pages = 829–835
	\| doi = 10.1111/j.1432-1033.1993.tb17986.x\| pmid = 8100523 \| url =		\| doi = 10.1111/j.1432-1033.1993.tb17986.x\| pmid = 8100523 \| url =
	}}</ref> ~~and the degradation of [[~~Glucagon-like peptide-1\|GLP-1]].<ref name=mentlein/><ref name="ahren2">{{cite journal		}}</ref> وتدرك Glucagon-like peptide-1 GLP-1 .<ref name=mentlein/><ref name="ahren2">{{cite journal
	\| last = Ahrén \| first = Bo \| coauthors = Landin-Olsson, Mona; Jansson, Per-Anders; Svensson, Maria; Holmes, David; Schweizer, Anja		\| last = Ahrén \| first = Bo \| coauthors = Landin-Olsson, Mona; Jansson, Per-Anders; Svensson, Maria; Holmes, David; Schweizer, Anja
	\| year = 2004 \| month = May \| accessdate = 2007-01-11		\| year = 2004 \| month = May \| accessdate = 2007-01-11
سطر 76:		سطر 79:
	\| doi = 10.1210/jc.2003-031907\| pmid = 15126524 \| url = http://jcem.endojournals.org/cgi/content/full/89/5/2078		\| doi = 10.1210/jc.2003-031907\| pmid = 15126524 \| url = http://jcem.endojournals.org/cgi/content/full/89/5/2078
	}}</ref>		}}</ref>
			<!--
	Bristol-Myers Squibb announced on 27 December 2006 that [[Otsuka Pharmaceutical Co.]] has been granted exclusive rights to develop and commercialize the compound in Japan. Under the licensing agreement, Otsuka will be responsible for all development costs, but Bristol-Myers Squibb retains rights to co-promote saxagliptin with Otsuka in Japan.<ref>{{cite press release		Bristol-Myers Squibb announced on 27 December 2006 that [[Otsuka Pharmaceutical Co.]] has been granted exclusive rights to develop and commercialize the compound in Japan. Under the licensing agreement, Otsuka will be responsible for all development costs, but Bristol-Myers Squibb retains rights to co-promote saxagliptin with Otsuka in Japan.<ref>{{cite press release
	\| title = Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd. Announce Exclusive Licensing Agreement for Diabetes Compound Saxagliptin in Japan		\| title = Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd. Announce Exclusive Licensing Agreement for Diabetes Compound Saxagliptin in Japan
سطر 134:		سطر 137:
	*[[Development of dipeptidyl peptidase-4 inhibitors]]		*[[Development of dipeptidyl peptidase-4 inhibitors]]


			-->
	==المصادر==		==المصادر==
	{{reflist}}		{{reflist}}
سطر 142:		سطر 147:
	*[http://www.forbes.com/2004/01/26/cx_mh_rl_diabetestearsheet_5.html The race to get DPP-4 inhibitors to market] - Forbes.com		*[http://www.forbes.com/2004/01/26/cx_mh_rl_diabetestearsheet_5.html The race to get DPP-4 inhibitors to market] - Forbes.com
	*{{cite web\|url=http://www.medpagetoday.com/Washington-Watch/Washington-Watch/13555\|title=Saxagliptin First Diabetes Drug to Pass FDA Cardiovascular Safety Review\|last=Walker\|first=Emily P.\|work=}}		*{{cite web\|url=http://www.medpagetoday.com/Washington-Watch/Washington-Watch/13555\|title=Saxagliptin First Diabetes Drug to Pass FDA Cardiovascular Safety Review\|last=Walker\|first=Emily P.\|work=}}
	~~-->~~
	{{بذرة}}		{{بذرة}}
	{{Oral hypoglycemics}}		{{Oral hypoglycemics}}

إدارة الموسوعة: إخفاء النص الإنكليزي لترجمته لاحقاً بكود

2013-03-27T10:23:04Z

إخفاء النص الإنكليزي لترجمته لاحقاً بكود

→ مراجعة أقدم		مراجعة 10:23، 27 مارس 2013
سطر 50:		سطر 50:
	\| StdInChIKey = QGJUIPDUBHWZPV-SGTAVMJGSA-N		\| StdInChIKey = QGJUIPDUBHWZPV-SGTAVMJGSA-N
	}}		}}
			الساكساغلبتين {{إنج\|Saxagliptin}} ([[International Nonproprietary Name\|rINN]]) سمي سابقاً '''BMS-477118''' وهو دواء فموي لمرض السكري من مثبطات DPP-4
			<!--
	'''Saxagliptin''' ([[International Nonproprietary Name\|rINN]]), previously identified as '''BMS-477118''', is a new oral hypoglycemic ([[anti-diabetic drug]]) of the new [[DPP-4 inhibitors\|dipeptidyl peptidase-4 (DPP-4) inhibitor]] class of drugs.<ref name="ahren">{{cite journal \| author = Augeri D ''et al.''		'''Saxagliptin''' ([[International Nonproprietary Name\|rINN]]), previously identified as '''BMS-477118''', is a new oral hypoglycemic ([[anti-diabetic drug]]) of the new [[DPP-4 inhibitors\|dipeptidyl peptidase-4 (DPP-4) inhibitor]] class of drugs.<ref name="ahren">{{cite journal \| author = Augeri D ''et al.''
	\| title = Discovery and preclinical profile of Saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes		\| title = Discovery and preclinical profile of Saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
سطر 141:		سطر 142:
	*[http://www.forbes.com/2004/01/26/cx_mh_rl_diabetestearsheet_5.html The race to get DPP-4 inhibitors to market] - Forbes.com		*[http://www.forbes.com/2004/01/26/cx_mh_rl_diabetestearsheet_5.html The race to get DPP-4 inhibitors to market] - Forbes.com
	*{{cite web\|url=http://www.medpagetoday.com/Washington-Watch/Washington-Watch/13555\|title=Saxagliptin First Diabetes Drug to Pass FDA Cardiovascular Safety Review\|last=Walker\|first=Emily P.\|work=}}		*{{cite web\|url=http://www.medpagetoday.com/Washington-Watch/Washington-Watch/13555\|title=Saxagliptin First Diabetes Drug to Pass FDA Cardiovascular Safety Review\|last=Walker\|first=Emily P.\|work=}}
			-->
	{{بذرة}}		{{بذرة}}
	{{Oral hypoglycemics}}		{{Oral hypoglycemics}}

إدارة الموسوعة: نقل النص للترجمة

2013-03-26T13:23:02Z

نقل النص للترجمة

صفحة جديدة

{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 459811747
| IUPAC_name = (1''S'',3''S'',5''S'')-2-[(2''S'')-2-amino-2-(3-hydroxy-1-adamantyl)<br>acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile
| image = Saxagliptin.svg


| tradename =
| Drugs.com = {{drugs.com|CDI|saxagliptin}}
| MedlinePlus = a610003
| licence_EU = Onglyza
| licence_US = Saxagliptin
| pregnancy_category =
| legal_UK = POM
| legal_US = Rx-only
| legal_status =
| routes_of_administration = Oral


| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| excretion =


| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 361442-04-8
| ATC_prefix = A10
| ATC_suffix = BH03
| PubChem = 11243969
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB06335
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 9419005
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = 8I7IO46IVQ
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 385517


| C=18 | H=25 | N=3 | O=2
| molecular_weight = 315.41 [[Gram|g]]/[[Mole (unit)|mol]]
| smiles = O=C(N1[C@H](C#N)C[C@@H]2C[C@H]12)[C@@H](N)C35CC4CC(C3)CC(O)(C4)C5
| InChI = 1/C18H25N3O2/c19-8-13-2-12-3-14(12)21(13)16(22)15(20)17-4-10-1-11(5-17)7-18(23,6-10)9-17/h10-15,23H,1-7,9,20H2/t10?,11?,12-,13+,14+,15-,17?,18?/m1/s1
| InChIKey = QGJUIPDUBHWZPV-SGTAVMJGBR
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C18H25N3O2/c19-8-13-2-12-3-14(12)21(13)16(22)15(20)17-4-10-1-11(5-17)7-18(23,6-10)9-17/h10-15,23H,1-7,9,20H2/t10?,11?,12-,13+,14+,15-,17?,18?/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = QGJUIPDUBHWZPV-SGTAVMJGSA-N
}}

'''Saxagliptin''' ([[International Nonproprietary Name|rINN]]), previously identified as '''BMS-477118''', is a new oral hypoglycemic ([[anti-diabetic drug]]) of the new [[DPP-4 inhibitors|dipeptidyl peptidase-4 (DPP-4) inhibitor]] class of drugs.<ref name="ahren">{{cite journal | author = Augeri D ''et al.''
| title = Discovery and preclinical profile of Saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
| journal = [[Journal of Medicinal Chemistry]] | volume = 48 | issue = 15 | pages = 5025–5037 | year = 2005
| pmid = 16033281| doi = 10.1021/jm050261p}}</ref> Early development was solely by [[Bristol-Myers Squibb]]; in 2007 [[AstraZeneca]] joined with Bristol-Myers Squibb to co-develop the final compound and collaborate on the marketing of the drug. A New Drug Application for saxagliptin in the treatment of type 2 diabetes was submitted to the FDA in June 2008. It was based on a drug development program with 8 randomized trials: 1 phase 2 dose-ranging (2.5–100 mg/d) study; 6 phase 3, 24-week controlled trials with additional controlled follow-up from 12 to 42 months, double-blinded throughout; and one 12-week mechanism-of-action trial with a 2-year follow-up period.<ref name="Postgraduate Medicine 2010">{{cite journal | author=Robert Frederich, MD, PhD et al. | title=A Systematic Assessment of Cardiovascular Outcomes in the Saxagliptin Drug Development Program for Type 2 Diabetes | journal=Postgraduate Medicine. | month=May | year=2010 | pages=16–27 | volume=122 | issue=3 | url=http://www.postgradmed.com/index.php?article=2138#none | doi=10.3810/pgm.2010.05.2138 | pmid=20463410}}</ref> In June 2008, it was announced that '''Onglyza''' would be the trade name under which saxagliptin will be marketed.<ref name="Bloomberg">{{cite news| url=http://www.bloomberg.com/apps/news?pid=20601103&sid=amRAcE.Jql6g&refer=news | work=Bloomberg | title=Bristol, Takeda Drugs Offer Alternatives to Januvia (Update2) | date=2008-06-07}}</ref>

The FDA approved Saxagliptin with brand name Onglyza on July 31, 2009.<ref>{{cite news
| author = Telegram | title = FDA approves diabetes drug from two area manufacturers
| url = http://www.telegram.com/article/20090802/NEWS/908020328/1002
| publisher = Worcester Telegram & Gazette Corp. | date = 2 August 2009 | accessdate = 2009-08-02
}}</ref>

Dipeptidyl peptidase-4's role in [[blood glucose]] regulation is thought to be through degradation of [[glucose-dependent insulinotropic peptide|GIP]]<ref name="mentlein">{{cite journal
| last = Mentlein | first = R | authorlink = | coauthors = Gallwitz, B; Schmidt, WE
| date = 15 June 1993 | accessdate = 2007-01-11
| title = Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum
| journal = [[European Journal of Biochemistry]] | volume = 214 | issue = 3 | pages = 829–835
| doi = 10.1111/j.1432-1033.1993.tb17986.x| pmid = 8100523 | url =
}}</ref> and the degradation of [[Glucagon-like peptide-1|GLP-1]].<ref name=mentlein/><ref name="ahren2">{{cite journal
| last = Ahrén | first = Bo | coauthors = Landin-Olsson, Mona; Jansson, Per-Anders; Svensson, Maria; Holmes, David; Schweizer, Anja
| year = 2004 | month = May | accessdate = 2007-01-11
| title = Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes
| journal = [[Journal of Clinical Endocrinology & Metabolism]] | volume = 89 | issue = 5 | pages = 2078–2084
| doi = 10.1210/jc.2003-031907| pmid = 15126524 | url = http://jcem.endojournals.org/cgi/content/full/89/5/2078
}}</ref>

Bristol-Myers Squibb announced on 27 December 2006 that [[Otsuka Pharmaceutical Co.]] has been granted exclusive rights to develop and commercialize the compound in Japan. Under the licensing agreement, Otsuka will be responsible for all development costs, but Bristol-Myers Squibb retains rights to co-promote saxagliptin with Otsuka in Japan.<ref>{{cite press release
| title = Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd. Announce Exclusive Licensing Agreement for Diabetes Compound Saxagliptin in Japan
| publisher = Bristol-Myers Squibb | date = December 27, 2006 | accessdate = 2006-12-27
| url = http://investor.bms.com/phoenix.zhtml?c=106664&p=irol-newsArticle&ID=944899&highlight=
}}</ref> Further, on 11 January 2007 it was announced that Bristol-Myers Squibb and [[AstraZeneca]] would work together to complete development of the drug and in subsequent marketing.<ref>{{cite news
| author = Associated Press | title = AstraZeneca teams with Bristol-Myers on diabetes drugs
| url = http://www.delawareonline.com/apps/pbcs.dll/article?AID=/20070111/BUSINESS/70111024/-1/NLETTER02
| publisher = Delaware News-Journal | date = 11 January 2007 | accessdate = 2007-01-11
}} {{Dead link|date=October 2010|bot=H3llBot}}</ref>

==التصنيع==
The synthesis of Saxagliptin by Bristol-Myers Squibb by the amide coupling of N-Boc-3-hydroxyadamantylglycine ('''2''') and methanoprolineamide ('''3''') with [[1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide|EDC]]. The former is commercially available, whereas the latter is available as the N-Boc analog. The prolineamide moiety is subsequently dehydrated with [[trifluoroacetic anhydride]] to give the cyanide as the trifluoracetate ester, which is hydrolyzed. Removal of the [[Boc anhydride|Boc protecting group]], followed by neutralization gives the desired product ('''1'''):<ref>{{cite journal | journal = [[Org. Process Res. Dev.]] | doi = 10.1021/op900226j | title = Preparation of Saxagliptin, a Novel DPP-IV Inhibitor | year = 2009 | pages = 091016152805096 | author8 = Scott A. Savage, Gregory S. Jones, Sergei Kolotuchin, Shelly Ann Ramrattan, Truc Vu, and Robert E. Waltermire | last1 = Savage | first1 = Scott A. | last2 = Jones | first2 = Gregory S. | last3 = Kolotuchin | first3 = Sergei | last4 = Ramrattan | first4 = Shelly Ann | last5 = Vu | first5 = Truc | last6 = Waltermire | first6 = Robert E. | volume = 13}}</ref>

:[[File:Production of saxagliptin.png|450px]]

==التأثير الدوائي==
Saxagliptin is part of a class of diabetes medications called [[dipeptidyl peptidase-4]] (DPP-4) inhibitors.
DPP-4 is an enzyme that breaks down [[incretin]] hormones. As a [[Dipeptidyl peptidase-4 inhibitor|DPP-4 inhibitor]], Saxagliptin slows down the breakdown of incretin hormones, increasing the level of these hormones in the body. It is this increase in incretin hormones that is responsible for the beneficial actions of Saxagliptin, including increasing insulin production in response to meals and decreasing the amount of glucose (sugar) that the liver produces.<ref>[http://diabetes.emedtv.com/onglyza/onglyza.html] Diabetes info</ref>

Because incretin hormones are more active in response to higher blood sugar levels (and are less active in response to low blood sugar), the risk of dangerously low blood sugar (hypoglycemia) is low with Saxagliptin.

==فعالية==
Oral saxagliptin 2.5 or 5 mg once daily suppresses DPP-4 activity for 24 hours,<ref name="auspre01">{{cite journal |title=New Drugs: Saxagliptin |journal=Australian Prescriber |year=2011 |month=June |issue=34 |pages=89–91 |url=http://www.australianprescriber.com/magazine/34/3/89/91 }}</ref> significantly improving mean HbA1c levels (relative to placebo) in well designed, 24-week trials in treatment-naive patients with type 2 diabetes.<ref name="saxa">{{cite journal | last1 = Dhillon | first1 = S | last2 = Weber | first2 = J. | year = 2009 | title = Saxagliptin| url = http://adisonline.com/drugs/abstract/2009/69150/Saxagliptin.5.aspx | journal = Drugs | pmid = 19791828 | volume = 69 | issue = 15| pages = 2103–2114 | doi = 10.2165/11201170-000000000-00000 }}</ref> Combination therapy with saxagliptin 5 mg once daily and metformin was more effective than saxagliptin or metformin monotherapy.<ref name="saxa" /> When the relative benefits of increasing the dose of a sulfonylurea or adding saxagliptin were assessed in a study of 768 patients, combination treatments were shown to have a significantly greater impact on fasting blood glucose than increasing the tested glibenclamide dose alone.<ref name="auspre01" />

==أمان الدواء==
In 4148 patients studied, 3 adverse reactions were seen higher in saxaglyptin vs placebo.
Table 1: Adverse Reactions (Regardless of Investigator Assessment of Causality) in Placebo-Controlled Trials* Reported in ≥ 5% of Patients Treated with ONGLYZA (saxagliptin tablets) 5 mg and More Commonly than in Patients Treated with Placebo.<ref name = rxlist>{{cite web | publisher = RxList | title = Onglyza | url = http://www.rxlist.com/onglyza-drug.htm | accessdate = 2012-01-31}}</ref>
{| class="wikitable" style="margin: 1em auto 1em auto;"
|+ '''Number (%) of Patients'''
! scope="col" |
! scope="col" | ONGLYZA 5 mg N=882
! scope="col" | Placebo N=799
|-
| Upper respiratory tract infection || 68 (7.7) || 61 (7.6)
|-
| Urinary tract infection || 60 (6.8) || 49 (6.1)
|-
| Headache || 57 (6.5) || 47 (5.9)<ref name = rxlist/>

|}

* The 5 placebo-controlled trials include two monotherapy trials and one add-on combination therapy trial with each of the following: metformin, thiazolidinedione, or glyburide. Table shows 24-week data regardless of glycemic rescue.<ref name = rxlist/>

In February 2012, Bristol-Myers/Astra Zeneca distributed additional safety information on saxaglyptin use in South Africa. The package insert is to be edited for South Africa. Contra-indications will now include a history of sensitivity to saxaglyptin (or an other DPP4 inhibitor) as well as pancreatitis. Spontaneously-reported adverse events in South Africa have included anaphylaxis, angioedema and acute pancreatitis.

==تحمل الدواء==
Both monotherapy and combination therapy with other agents was generally well tolerated in clinical trials.<ref name="saxa" />

==خطر الإصابة بالسرطان مع مثبطات PP-4 ==
The DPP-4 enzyme is known to be involved in the suppression of certain malignancies, particularly in limiting the tissue invasion of these tumours. Inhibiting the DPP-4 enzymes may allow some cancers to progress.<ref name="pmid15375776">{{cite journal | author = Pro B, Dang NH | title = CD26/dipeptidyl peptidase IV and its role in cancer | journal = Histol. Histopathol. | volume = 19 | issue = 4 | pages = 1345–51 | year = 2004 | month = October | pmid = 15375776 | doi = | url = http://www.hh.um.es/Abstracts/Vol_19/19_4/19_4_1345.htm | issn = }}</ref><ref name="pmid15735018">{{cite journal | author = Wesley UV, McGroarty M, Homoyouni A | title = Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway | journal = Cancer Res. | volume = 65 | issue = 4 | pages = 1325–34 | year = 2005 | month = February | pmid = 15735018 | doi = 10.1158/0008-5472.CAN-04-1852 | url = | issn = }}</ref> A study of DPP-4 inhibition in human non-small cell lung cancer (NSCLC) concluded that "DPPIV functions as a tumor suppressor, and its downregulation may contribute to the loss of growth control in NSCLC cells.<ref name="Wesley 1">{{cite journal | last = Wesley| first = U | coauthors = et al | year = 2004 | title = Role for dipeptidyl peptidase IV in tumor suppression of human non small cell lung carcinoma cells.| journal = [[Int J Cancer]] | volume = 109 | issue = 6 | pages = 855–866 | url = http://www.ncbi.nlm.nih.gov/pubmed/15027119 | doi = 10.1002/ijc.20091 | pmid = 15027119}}</ref>

The risk of cancer suppression with DPP-4 down-regulation applies to all the DPP-4 inhibitors on the market in addition to saxagliptin (sitagliptin and vildagliptin)

==انظر أيضاً==
*[[Dipeptidyl peptidase 4]]
*[[Development of dipeptidyl peptidase-4 inhibitors]]

==المصادر==
{{reflist}}

==روابط خارجية==
* [http://www.onglyza.com Official site]
* {{UTGlucagon|dpp4}}
*[http://www.forbes.com/2004/01/26/cx_mh_rl_diabetestearsheet_5.html The race to get DPP-4 inhibitors to market] - Forbes.com
*{{cite web|url=http://www.medpagetoday.com/Washington-Watch/Washington-Watch/13555|title=Saxagliptin First Diabetes Drug to Pass FDA Cardiovascular Safety Review|last=Walker|first=Emily P.|work=}}
{{بذرة}}
{{Oral hypoglycemics}}
[[تصنيف:أدوية]]
[[تصنيف:موسوعة الأدوية]]
[[Category:Dipeptidyl peptidase-4 inhibitors]]
[[Category:Nitriles]]
[[Category:Bristol-Myers Squibb]]
[[Category:Adamantanes]]
[[Category:Alcohols]]
[[Category:Amides]]
[[Category:Nitrogen heterocycles]]