NPH insulin
 | This articleneeds additional citations forverification.(November 2020) |
 A vial of NPH insulin withinsulin syringe | |
| Clinical data | |
|---|---|
| Trade names | Novolin N, Humulin N, Insulatard, others |
| Other names | Neutral protamine Hagedorn insulin,[1] protamine zinc insulin (slightly different),[2] isophane insulin,[2] compound insulin zinc suspension (slightly different),[2] intermediate-acting insulin |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682611 |
| Routes of administration | Subcutaneous |
| ATC code | |
| Legal status | |
| Legal status |
|
| Pharmacokineticdata | |
| Onset of action | 90 minutes[3] |
| Duration of action | 24 hours[3] |
| Identifiers | |
| CAS Number | |
| ChemSpider |
|
Neutral Protamine Hagedorn (NPH) insulin,also known asisophane insulin,is anintermediate-acting insulingiven to help controlblood sugar levelsin people withdiabetes.The words refer toneutral pH(pH = 7),protaminea protein, andHans Christian Hagedorn,the insulin researcher who invented this formulation. It is designed to improve the delivery of insulin, and is one of the earliest examples of engineered drug delivery.[3]
It is used by injection under the skin once to twice a day.[1]Onset of effects is typically in 90 minutes and they last for 24 hours.[3]Versions are available that come premixed with a short-acting insulin, such asregular insulin.[2]
The common side effect islow blood sugar.[3]Other side effects may include pain or skin changes at the sites of injection,low blood potassium,andallergic reactions.[3]Use duringpregnancyis relatively safe for the fetus.[3]NPH insulin is made by mixing regular insulin andprotaminein exact proportions withzincandphenolsuch that aneutral-pHis maintained andcrystalsform.[1]There are human and pig insulin based versions.[1]
Protamine insulin was first created in 1936 and NPH insulin in 1946.[1]It is on theWorld Health Organization's List of Essential Medicines.[4]NPH is an abbreviation for "neutral protamine Hagedorn".[1]In 2020, insulin isophane was the 221st most commonly prescribed medication in the United States, with more than 2million prescriptions.[5][6]In 2020, the combination of human insulin with insulin isophane was the 246th most commonly prescribed medication in the United States, with more than 1million prescriptions.[7][8]
Medical uses
[edit]NPH insulin is cloudy and has an onset of 1–3 hours. Its peak is 6–8 hours and its duration is up to 24 hours.[9]
It has an intermediate duration of action, meaning longer than that of regular and rapid-acting insulin, and shorter than long acting insulins (ultralente,glargineordetemir). A recent Cochrane systematic review[10]compared the effects of NPH insulin to otherinsulin analogues(insulin detemir,insulin glargine,insulin degludec) in both children and adults withType 1 diabetes.Insulin detemir appeared provide a lower risk of severe hyperglycemia compared to NPH insulin, however this finding was inconsistent across included studies.[10]In the same review no other clinically significant differences were found between different insulin analogues in either adults nor children.[10]
History
[edit]Hans Christian Hagedorn(1888–1971) andAugust Krogh(1874–1949) obtained the rights forinsulinfromFrederick BantingandCharles BestinToronto,Canada. In 1923 they formed Nordisk Insulin laboratorium, and in 1926 with August Kongsted he obtained a Danish royal charter as a non-profit foundation.
In 1936, Hagedorn and B. Norman Jensen discovered that the effects of injected insulin could be prolonged by the addition ofprotamineobtained from the "milt" orsemenof river trout. The insulin would be added to the protamine, but the solution would have to be brought to pH 7 for injection.University of Toronto,Canadalater licensed protamine zinc insulin (PZI),[11]to several manufacturers. This mixture only needs to be shaken before injection. The effects of PZI lasted for 24–36 h.
In 1946, Nordisk was able to form crystals of protamine and insulin and marketed it in 1950, as neutral protamine Hagedorn (NPH) insulin. NPH insulin has the advantage that it can be mixed with an insulin that has a faster onset to complement its longer lasting action.[medical citation needed]
Eventually all animal insulins made by Novo Nordisk were replaced by synthetic,recombinant"human" insulin.[medical citation needed]Synthetic "human" insulin is also complexed with protamine to form NPH.[medical citation needed]
Timeline
[edit]The timeline is as follows:[citation needed]
- 1926 Nordisk receives Danish charter to produce insulin
- 1936 Hagedorn discovers that adding protamine to insulin prolongs the effect of insulin
- 1936 Canadians D.M. Scott and A.M. Fisher formulate zinc insulin mixture and license toNovo
- 1946 Nordisk crystallizes a protamine and insulin mixture
- 1950 Nordisk markets NPH insulin
- 1953 Nordisk markets "Lente" zinc insulin mixtures.
Society and culture
[edit]Names
[edit]Brand names include Humulin N, Novolin N, Novolin NPH, Gensulin N, SciLin N, Insulatard, and NPH Iletin II.[citation needed]
See also
[edit]References
[edit]- ^abcdefOwens DR (1986).Human Insulin: Clinical Pharmacological Studies in Normal Man.Springer Science & Business Media. pp. 134–136.ISBN9789400941618.Archivedfrom the original on 2017-01-18.
- ^abcdBritish national formulary: BNF 69(69 ed.). British Medical Association. 2015. pp. 464–472.ISBN9780857111562.
- ^abcdefg"Insulin Human".The American Society of Health-System Pharmacists.Archivedfrom the original on 22 October 2016.Retrieved8 January2017.
- ^World Health Organization(2019).World Health Organization model list of essential medicines: 21st list 2019.Geneva: World Health Organization.hdl:10665/325771.WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- ^"The Top 300 of 2020".ClinCalc.Retrieved7 October2022.
- ^"InsulinIsophane - Drug Usage Statistics".ClinCalc.Retrieved7 October2022.
- ^"The Top 300 of 2020".ClinCalc.Retrieved7 October2022.
- ^"Insulin Human; Insulin Isophane Human - Drug Usage Statistics".ClinCalc.Retrieved7 October2022.
- ^"NPH insulin | DrugBank Online".go.drugbank.com.Retrieved2022-09-09.
- ^abcHemmingsen B, Metzendorf MI, Richter B (March 2021)."(Ultra-)long-acting insulin analogues for people with type 1 diabetes mellitus".The Cochrane Database of Systematic Reviews.3(3): CD013498.doi:10.1002/14651858.cd013498.pub2.PMC8094220.PMID33662147.
- ^"The History of Insulin"(PDF).Karger.com/.Basel, Switzerland: Karger Publishers. Archived fromthe original(PDF)on March 4, 2016.RetrievedJune 10,2015.
