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Huminsulin L
Lente by Eli Lilly
intermediate-acting
r-DNA/GE/GM
U40, U100 Zinc
Action in dogs:
  • onset 2-10h,
  • peak 6-24h,
  • duration 14-24h
Line: Humulin
Also known as: Huminsulin Long, Humutard, Humulin L, Humulin Lenta, Humulin Lente
Humulina L, Humuline Long, Umuline Lente, Umuline Zinc Compose
Similar to: Monotard, Novolin L

Names of Lilly r-DNA/GE/GM insulins worldwide
Use and Handling:
Shelf Life: 24 months Type: cloudy
When Opened: 28 days room temp.
In Pen: N/A
Notes: Protect from light and heat
Do Not Freeze, Resuspend
Do not use if product does not re-suspend
Do not use intravenously [1]
store at 2-8C


Lentetap

Time activity profile for Lente insulins.


Note that some countries have the brand name in U40 strength.

Huminsulin L [2] was a U100 r-DNA/GE/GM intermediate-acting, lente insulin. [3][4][5] It was known elsewhere as Umuline Zinc Compose, Humulin L and Humuline Long. Novo Nordisk also made similar insulins, calling them Novolin L [6] and Monotard. [7][8]

Humulin L came to an end when Eli Lilly announced in July, 2005 that it would no longer be produced. [9][10] The UK & Euro production of Humulin L stopped a year prior to this, in July 2004. [11][12]

Why Lente doesn't equal 70/30[]

Lente-70 30

Direct comparison of insulin activity profiles for Lente and 70/30 insulins. The early strong action from the non-suspended R/neutral/normal insulin is seen at the "bump" from hours 0-6.

Let's look at the differences in the two insulins. Lente is comprised of 70 % long-acting Ultralente insulin and 30% short-acting Semilente insulin.[13] So proportions of a long-acting and short-acting insulin are being combined to produce a intermediate-acting insulin. Both Ultralente and Semilente insulin are suspended by adding zinc and the size of their respective insulin crystals. The largest insulin crystals are those of Ultralente, while Semilente contains the smallest, or microcrystals. Simply put, you're combining a long insulin and a short insulin to make an intermediate-acting one.[14]

70/30 insulin starts with 70% NPH/isophane insulin, an intermediate-acting insulin which is suspended by protamine. To that, 30% R/neutral/normal insulin, which is short-acting and soluble, meaning there is no suspension; nothing is added to this insulin to delay its action. In this case, you are taking an intermediate-acting insulin with a suspension and adding to it a short-acting one with no suspension to create an intermediate-acting insulin.

So we have an insulin (Lente), made up of a long-acting and short-acting insulin, both with zinc suspensions, and a mixed insulin (70/30), made from an intermediate-acting protamine suspended insulin and a short-acting one without any suspension. Because of these differences, the insulin action profile for these two insulins is going to be quite different, even though both insulins are classed as intermediate-acting.

What Lente Is Not[]

No Lente-type insulin regardless of species can contain any NPH/isophane insulin [15] or any R/Neutral insulin. [16][17]

Both are chemically impossible: the phenol preservative present in NPH/isophane alters the action of Lente-type insulins, creating a mixture with an approximate action of R/Neutral. [18][19]

The zinc suspension of Lente-type insulin binds R/Neutral, causing the short-acting insulin to slow, losing its short-acting effect. [20][21]

Before the invention of VetPen, Lente-type insulins could not be dispensed in pen or cartridge form because the glass ball formerly used to mix the insulin in these devices shattered the Lente crystals.[22]

Combining Lente Family Insulins[]

None of the Lente family of insulins (semilente, Lente, Ultralente) can be combined with [23] NPH/isophane insulins. The phenol preservatives present in NPH-type insulins alters the Lente-types to the point where they become a close approximation of R/neutral, with regard to action [24].

Keeping the phenol preservatives in mind, all protamine-suspended insulin mixes would be "off limits" regarding same syringe mixing with any Lente-type insulins [24].


Insulin manufacturers [25] indicate that R/neutral and semilente, Lente, ultralente insulins are able to be combined in the same syringe, but only just before injection. In pre-filled syringes, the zinc suspension of the Lente-type insulins binds the R/neutral, causing it to lose its short-acting effect. Various studies have documented this, and some doctors advise against using R/neutral in the same syringe with the Lente family of insulins [17][26][27][24].


The following are lente type zinc suspension insulins but since they are produced for use in animals, they are not found in BNF, but in its sister veterinary formulary.

These fall into the category of intermediate-length insulins.

The Novo insulins,Monotard and Ultratard, were available slightly longer in Europe. [30]

From the announcement: Monotard and Ultratard will not be available in the UK after February 2006. The discontinuation of these insulins was initially announced in September 2004. Initially the discontinuation was scheduled for February 2006, however this date has now been brought forward to October 2005.

Compared to Humulin N[]

Humulin L/Monotard and Humulin N are both U100 strength insulins of r-DNA/GE/GM species. They differ in their suspension. Humulin L and Monotard were Zinc suspended, from the Lente type family, while Humulin N/NPH insulins are isophane suspended.

References[]

  1. Maddison, Jill E.,Page, Stephen W.,Church, David B. (2008). Small Animal Clinical Pharmacology. Saunders Ltd..
  2. Humulin L carton photo..
  3. Patient Leaflet-Humulin L. Eli Lilly.
  4. Humulin L Carton Photo.
  5. Definition of Lente Insulin. Merck Manual.
  6. Novolin L Discontinuation Notice. US Food and Drug Administration (2003).
  7. Scientific Discussion-Monotard. EMEA.
  8. Monotard Discontinuation Notice. Diabetes UK (July 2005).
  9. Humulin L Discontinuation Notice. Eli Lilly (2005).
  10. Lilly US Humulin L/Humulin U Discontinuation Sheet. Eli Lilly.
  11. Withdrawal of EU/UK Humulin L. Diabetes UK (July 2004).
  12. Lilly EU/UK Product Sheet & Time Activity Profiles. Eli Lilly.
  13. Dumitriu, Severian (2001). Polymeric Biomaterials, Revised and Expanded 1104. CRC Press.
  14. Greco, Deborah (2010). Treating Diabetes Mellitus in Dogs and Cats. Western Veterinary Conference.
  15. Combining Lente-type Insulins with Phenol-Preserved Insulins. National Federation for the Blind.
  16. Lente Zinc Suspension Causes Loss Of R/Neutral Short-Acting Effect. Endotext.org.
  17. 17.0 17.1 Huffman DM, Garber AJ. (1991). Availability of Soluble (R/Neutral) Insulin in Mixed Preparations With Crystalline (Lente) & Ultralente GE Insulin. Clinical Therapeutics. Cite error: Invalid <ref> tag; name "Huffman" defined multiple times with different content
  18. Lente-Type Insulins & NPH/Isophane Insulins-A Bad Combination. National Federation for the Blind.
  19. Havlik I, Galasko G, Alberts E, Furman KI, Seftel HC. (1988). Solubility Changes on Mixing Short- and Long-acting Insulin Preparations. South African Medical Journal.
  20. Deckert T. (1980). Intermediate-Acting Insulin Preparations: NPH (Isophane) & Lente. Diabetes Care.
    Note--in 1980, there were no r-DNA/GE/GM insulins
  21. Resource Guide. American Diabetes Association (2005).
  22. Hanas, Ragnar (1999). Insulin-Dependent Diabetes--Page 10. Children With Diabetes.
  23. Phenol Preservatives & Lente-type Insulins--A Bad Combination. National Federation for the Blind.
  24. 24.0 24.1 24.2 Insulin Therapy-Mixing Precautions. RxEd.org.
  25. Insulin Producers vs Doctors Re:Combining R/Neutral & Lente-type Insulins. Endotext.org.
  26. Bilo HJ, Heine RJ, Sikkenk AC, van der Meer J, van der Veen EA. (1987). Absorption Kinetics & Action Profiles-Single Subcutaneous Administration of Human Soluble (R/Neutral) & Lente Insulin. Diabetes Care.
  27. Heine RJ, Sikkenk AC, Eizenga WH, van der Veen EA. (1983). Delayed Onset of Action of Soluble (R/Neutral) Insulin After Premixing With Lente Insulin. Diabetes Research & Clinical Practice.
  28. Iletin I Lente-Beef/Pork Insulin Shown at Right.
  29. Carton Image-Iletin II Lente.
  30. Monotard Discontinuation Notice. Diabetes UK (July 2005).

More Information[]


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