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词条 Insulin aspart
释义

  1. Medical uses

      Onset of action  

  2. Side effects

  3. Chemical properties

  4. Formulations

      Temperature    Variations  

  5. References

{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 464363109
| IUPAC_name =
| image = Insulin Aspart Structural Formula.gif
| drug_name = Insulin Aspart
| tradename = NovoLog, NovoRapid, Fiasp, others
| Drugs.com = {{drugs.com|monograph|insulin_aspart}}
| MedlinePlus = a605013
| pregnancy_AU =
| pregnancy_US = C
| pregnancy_category =
| legal_AU =
| legal_CA =
| legal_UK = POM
| legal_US = Rx-only
| legal_status =
| routes_of_administration = Subcutaneous, intravenous
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| excretion =
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = none
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 116094-23-6
| ATC_prefix = A10
| ATC_suffix = AB05
| PubChem = 16132418
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01306
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = D933668QVX
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D04475
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1201496
| C=256 | H=381 | N=65 | O=79 | S=6
| molecular_weight = 5825.8 g/mol
|alt=|caption=|type=|licence_EU=yes|licence_US=}}Insulin aspart, sold under the brand name Novolog among others, is a type of manufactured insulin used to treat type I and type II diabetes.[1] Typically it is taken just before eating.[1] It is generally used by injection under the skin but may also be used by injection into a vein.[1] Maximum effect occurs after about 2 hours and lasts for 4 hours.[1] Generally a longer acting insulin like NPH is also needed.[1]

Common side effects include low blood sugar, allergic reactions, itchiness, and pain at the site of injection.[1] Other serious side effects may include low blood potassium.[1] Use in pregnancy and breastfeeding is generally safe.[1] It works the same as human insulin by increasing the amount of glucose that tissues take in and decreasing the amount of glucose made by the liver.[2] It is a manufactured form of human insulin; where a single amino acid has been changed.[3]

Insulin aspart was approved for medical use in the United States in 2000.[2] In the United Kingdom it costs the NHS about 1.89 £ per 100 units as of 2019.[4] In the United States the wholesale cost of this amount is about 30 USD.[5] In 2016 it was the 87th most prescribed medication in the United States with more than 8 million prescriptions.[6] Manufacturing involves yeast, which have had the gene for insulin aspart put into their genome.[7] These yeast than make the insulin, which is harvested from the bioreactor.[8]

Medical uses

There is a lack of compelling evidence to conclude superiority of insulin aspart over human insulin.[9] It is thus unclear why the shifting of people from human insulin to this insulin aspart.[10]

Onset of action

The onset of action is approximately 15 minutes, the peak action is reached in 45–90 minutes, and the duration is 3–5 hours. However, as with all insulin, these numbers are based on averages, and vary between individuals due to blood flow, injection site, temperature and exercise.[19][11]

Side effects

The safety of insulin aspart in people with diabetes is not different than regular insulin. The side effects that are commonly associated with insulin therapy include: allergic reactions, injection site irritation, rashes, and hypoglycemia.[12] The most common side effect is hypoglycemia. Long-term use of insulin, including insulin aspart, can cause lipodystrophy at the site of repeated injections or infusion. To reduce the risk of lipodystrophy, rotate the injection sites within the same region. Weight gain can also occur with the use of insulin aspart and it has been attributed to anabolic effects of insulin and a decrease in glucosuria. Use of insulin aspart has also been associated with sodium retention and edema.[13]

Chemical properties

{{Refimprove section|date=December 2018}}

The components of insulin aspart are as follows:

  • Metal ion – zinc (19.6 μg/mL)
  • Buffer – disodium hydrogen phosphate dihydrate (1.25 mg/mL)
  • Preservatives – 3-methylphenol (m-cresol) (1.72 mg/mL) and phenol (1.50 mg/mL)
  • Isotonicity agents – glycerin (16 mg/mL) and sodium chloride (0.58 mg/mL).

The pH of insulin aspart is 7.2–7.6.[14]

Formulations

Insulin aspart can be used in insulin pump and insulin pen for subcutaneous injection. Additionally, it can be used with an injection port such as the I-port.[15]

Insulin aspart has a more rapid onset, and a shorter duration of activity than normal human insulin. Therefore, insulin aspart given by injection should normally be used in a regimen with long-acting or intermediate insulin.[16] Insulin aspart can also be used with external insulin pumps. The insulin in reservoirs of insulin pumps and infusion sets should be changed every 48 hours to avoid insulin degradation and loss of preservative.[11]

Temperature

It has been debated whether or not insulin aspart should be kept refrigerated at all times. The manufacturer claims it can last 28 days without refrigeration, as long as it is kept below 86 °F / 30 °C.[17] Above these temperatures, the potency of the insulin quickly degrades, rendering it less effective.

Variations

NovoLog Mix 70/30 is a product which contains 30% insulin aspart and 70% insulin aspart protamine. The insulin aspart protamine portion is a crystalline form of insulin aspart, which delays the action of the insulin, giving it a prolonged absorption profile after injection. The combination of the fast-acting form and the long-acting form allows the patient to receive fewer injections over the course of the day.[18]

The components of NovoLog Mix 70/30 are as follows:

  • Metal ion – zinc (19.6 μg/mL)
  • Buffer – dibasic sodium phosphate (1.25 mg/mL)
  • Preservatives – m-cresol (1.72 mg/mL) and phenol (1.50 mg/mL)
  • Isotonicity agents – sodium chloride (0.58 mg/mL) and mannitol (36.4 mg/mL)
  • Modifying protein – protamine (0.33 mg/mL)

The pH is 7.2–7.44.[14]

NovoLog Mix is marketed to be used with the Novo Nordisk FlexPen.[19] The onset of action is less than 30 minutes, the peak action is reached in 1–4 hours, and the duration is less than 24 hours.[14] NovoLog Mix is marketed in some countries as NovoMix 30.[20]

References

1. ^{{cite web |title=Insulin aspart Pregnancy and Breastfeeding Warnings |url=https://www.drugs.com/pregnancy/insulin-aspart.html |website=Drugs.com |accessdate=3 March 2019 |language=en}}
2. ^{{cite web |title=Insulin Aspart Monograph for Professionals |url=https://www.drugs.com/monograph/insulin-aspart.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |accessdate=3 March 2019 |language=en}}
3. ^{{cite book |last1=Turner |first1=J. Rick |title=New Drug Development: An Introduction to Clinical Trials: Second Edition |date=2010 |publisher=Springer Science & Business Media |isbn=9781441964182 |page=32 |url=https://books.google.ca/books?id=Rv10neRV3R8C&pg=PA32 |language=en}}
4. ^{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=697|edition=76}}
5. ^{{cite web |title=NADAC as of 2019-02-27 |url=https://data.medicaid.gov/Drug-Pricing-and-Payment/NADAC-as-of-2019-02-27/s7c9-pfa6 |website=Centers for Medicare and Medicaid Services |accessdate=3 March 2019 |language=en}}
6. ^{{cite web |title=The Top 300 of 2019 |url=https://clincalc.com/DrugStats/Top300Drugs.aspx |website=clincalc.com |accessdate=22 December 2018}}
7. ^{{cite book |last1=Banga |first1=Ajay K. |title=Therapeutic Peptides and Proteins: Formulation, Processing, and Delivery Systems, Second Edition |date=2005 |publisher=CRC Press |isbn=9781420039832 |page=13 |url=https://books.google.ca/books?id=CckrBgAAQBAJ&pg=PA13 |language=en}}
8. ^{{cite book |last1=Schmid |first1=Rolf D. |last2=Schmidt-Dannert |first2=Claudia |title=Biotechnology: An Illustrated Primer |date=2016 |publisher=John Wiley & Sons |isbn=9783527677566 |page=222 |url=https://books.google.ca/books?id=V5bNCwAAQBAJ&pg=PA222 |language=en}}
9. ^Insulin aspart for diabetes mellitus http://www.ti.ubc.ca/fr/insulin-aspart-diabetes-mellitus-last-update-march-2007
10. ^{{cite journal |doi=10.1136/bmj.c7139 |pmid=21159773 |title=How small changes led to big profits for insulin manufacturers |journal=BMJ |volume=341 |pages=c7139 |year=2010 |last1=Cohen |first1=D |last2=Carter |first2=P }}
11. ^FDA. NovoLog Insulin Aspart (rDNA origin) Injection. 7 June 2000. http://www.accessdata.fda.gov/drugsatfda_docs/label/2000/20986lbl.pdf
12. ^{{cite web |url=http://www.novolog.com/questions-default.asp?s=faqs-6 |title=Novolog: most FAQ |accessdate=2011 |website= }}
13. ^{{cite web |url=http://www.novo-pi.com/novolog.pdf |title=Novolog: insulin aspart (rDNA origin) injection |accessdate=October 2010 |website= }}
14. ^Crommelin DJA, Sindelar RD, Meibohm B. 2008. Pharmaceutical Biotechnology: Fundamentals and Applications. New York, NY: Informa Healthcare USA, Inc. p 270.
15. ^{{cite web|url=https://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a605013.html |title=Aspart insulin (rDNA origin) injection |accessdate=2007-06-08 |website= |archiveurl=https://web.archive.org/web/20070610074313/http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a605013.html |archivedate=2007-06-10 |deadurl=yes |df= }}
16. ^{{cite web |url=http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4254b_13_04_KP%20InsulinAspartFDAlabel102005.pdf |title=Novolog: insulin aspart |accessdate= |website= }}
17. ^{{cite web|url=https://www.novolog.com/type-2-diabetes/considering-novolog/novolog/novolog-storage.html |title=insulin aspart Storage |publisher=Novolog.com |date= |accessdate=2016-04-23}}
18. ^Rx List: NovoLog Mix 70/30. 6 August 2008. http://www.rxlist.com/novolog-mix-70-30-drug.htm
19. ^Novo Nordisk: NovoLog Mix 70/30. 2008. http://www.novologmix70-30.com/starting-with-novolog-mix.asp
20. ^{{cite web|url=http://www.medicines.org.uk/EMC/medicine/8591/SPC/NovoMix+30+Penfill+100+U+ml,+NovoMix+30+FlexPen+100+U+ml/|title=NovoMix 30 Penfill 100 units/ml, NovoMix 30 FlexPen 100 units/ml - Summary of Product Characteristics (SmPC) - (eMC)|author=|date=|website=www.medicines.org.uk}}
{{Oral hypoglycemics and insulin analogs}}{{Signaling peptide/protein receptor modulators}}

7 : RTT|Insulin receptor agonists|Insulin therapies|Diabetes|Human proteins|Recombinant proteins|Peptide hormones

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