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Long acting

All PZI's are long-acting insulins with activity profiles similar to this.

1975 Lilly JAMA ad

From left-insulins Semilente ("S"), Protamine Zinc ("P"), NPH/isophane ("N"), Regular/neutral/normal ("R"), Lente ("L"), and Ultralente ("U").


Various types of veterinary insulins are known as PZI, "Protamine Zinc Insulin".  [1] The ones we use most often for animals are a combination pork/beef-derived insulin or a beef-derived insulin. Because most are veterinary insulins, PZIs are not available at normal human pharmacies.

The only PZI insulin still available for people is CP Pharma's Hypurin Bovine Protamine Zinc and it must be imported from the UK.

PZI veterinary insulins are intermediate-acting to long-acting, and can be closer in molecular structure to a cat or dog's own insulin than human-type or analog insulins. PZI is rarely used in dogs but is considered when other insulins are not effective. [2][3][4] An R-DNA/GE/GM U 40 manufactured PZI, ProZinc, has just been approved in the US for use in cats; it has not been studied in dogs. [5]

PZI itself was introduced in 1936; it was the first insulin having any type of suspension [6]. But the combination of insulin and protamine produced by Novo Nordisk's Hagedorn and his colleagues was not stable and required patients to add a neutralizing liquid to the vial before it could be used. By 1938, Canadians D. A. Scott and A. M. Fisher discovered adding zinc to the mixture stabilized the insulin so that it only needed to be resuspended before being used. [7][8] Before PZI, the only insulin available was R/Neutral, having no additives to alter or extend its action. Until then, many with diabetes had to get up during the night to take an insulin injection because R/Neutral did not last long enough for an uninterrupted night's sleep. [9]


Use and HandlingEdit

According to the UK's National Health Service, [10] in cases where a shorter-acting insulin is needed in addition to the PZI, the protamine zinc insulin must always be injected separately--NO mixing--due to the excess of protamine in the insulin formula. [11][10][12][13]

Technical detailsEdit

PZI contains more zinc and protamine than NPH/isophane insulin and it is primarily the extra protamine which gives it its long-acting duration.[14] The additional protamine in the suspension [15] must first be broken down by proteolytic enzymes AKA proteases, [16] before the insulin in PZI can be absorbed. NPH/isophane insulin contains less protamine than PZI does and because there's less, it is an intermediate-acting insulin.

No Combining For PZIEdit

No Combining For PZI

Protamine Zinc PZI [17] insulin cannot be combined with other insulins, due to the amount of protamine in the insulin's formula. [18][10][19][13]


Specifications of PZIEdit

British National Formulary defines protamine zinc insulin as a sterile suspension of insulin in the form of a complex obtained by the addition of a suitable protamine and zinc chloride.

British Pharmacoepia (BP) and United States Pharmacoepia (USP) definitions: [21]

Protamine Zinc Insulin

Sterile buffered suspension of mammalian insulin to which protamine and zinc chloride are added. White suspension. pH 6.9 - 7.5 iso-osmotic with blood. Contains for each 100 units of insulin, 1 - 1.7 mg of protamine sulphate and zinc chloride equivalent to 200 per g of zinc, 10 - 11 mg of sodium phosphate.

Protamine Zinc Insulin

Buffered sterile suspension to which zinc chloride and protamine sulphate are added. 40, 80, 100 units/ml. Also contain glycerol, cresol, phenol, sodium phosphate for each 100 units of insulin in addition to protamine and zinc.

Types of Veterinary PZIEdit

ManufacturedEdit

These are manufactured, not compounded, insulins. This means the insulin keeps longer, and is less likely to vary, as compounded insulins can, from batch to batch. The manufactured insulins have a shelf life of three years (unopened).

BovineEdit

Insuvet PZI Edit

All Insuvet insulins have been discontinued by Pfizer Animal Health.[22][23][24] The insulins were made under contract by Wockhardt UK for both Pfizer and for Schering-Plough Animal Health, who owned the brand name earlier. Wockhardt makes the same insulins under their Hypurin brand name.[25]

VMD-No Further Supplies of Insuvet Insulins

Switching from Insuvet to Caninsulin

91 main

Insuvet Protamine Zinc--pure beef U100 PZI insulin.

Insuvet Protamine Zinc or Insuvet PZI was a PZI from Insuvet, similar to BCP's PZI above. Insuvet also made two other veterinary insulins.

Schering-Plough Animal Health contracted CP Pharma to produce its Insuvet line of bovine insulins. [25] The Insuvet line was sold to Pfizer Animal Health and it is believed that Pfizer continued to contract CP/Wockhardt UK for their production.

CP Pharma is based in the UK and is now the only supplier of manufactured bovine PZI. In other countries, you can import insulin from them or, if you are in North America, the compounded PZI in various strengths available from BCP and VPOA (US) and Summit (Canada).

CP Pharma Edit

69 main

Hypurin Bovine Protamine Zinc-U100 all-beef PZI insulin.

Hypurin Bovine Protamine Zinc is a U100 100% bovine PZI manufactured by CP Pharma. It is approved for use in [29] humans and can be imported into the US and other countries.

CP Pharma also produced Hypurin Vet Protamine Zinc, which was pure beef but not offered outside of the UK.

Those CP Pharma insulins are comparable to Insuvet Protamine Zinc, by Pfizer Animal Health, formerly by Schering-Plough Animal Health, a U100, 100% bovine PZI for veterinary use that is only available in the UK.

CP Pharma actually produced the Schering-Plough Animal Health Insuvet insulins. [25] After the Insuvet line was sold to Pfizer Animal Health, it's believed that Pfizer continued to contract CP/Wockhardt UK for their production.


R-DNA/GE/GMEdit

BI Animal HealthEdit

A recently approved R-DNA/GE/GM protamine zinc U 40 insulin for cats is ProZinc. ProZinc has not been studied in dogs. [30]


CompoundedEdit

Compounded insulins typically have shorter lifespans and there are fewer quality controls in place than with manufactured insulins to ensure the highest consistency insulin reaches the consumer.

BCP PZI Edit

BCP PZI is a bovine-origin PZI-based insulin. Because it's beef based, its amino acid chain is almost the same as that of a cat, so it's especially well-matched to cats.

BCP Veterinary Pharmacy [31] in Houston, TX, USA, manufactures and is the sole source supplier for BCP PZI. BCP PZI is a compounded insulin.

VPOA PZI Edit

All-Beef 40U PZI insulin is available from Veterinary Pharmacies of America in Houston, Texas, a source recommended by Dr. E. Hodgkins. [32]

BCP, VPOA, and other compounding pharmacies are the only US source for pure beef insulin of any type. Manufactured beef insulins must be imported from CP Pharma.

Porcine PZIEdit

Stokes compounding pharmacy in New Jersey is now offering compounded porcine (pork) PZI insulin.[33][34] Stokes offers its bovine (beef) PZI insulin in both U100 and U40 strengths; it's likely their pork PZI would also be available in both insulin strengths.[35]

UK, Canada, and US-other compounded PZIs Edit

Those in Canada can obtain 100% beef compounded PZI in U100 strength from Summit Veterinary Pharmacy [36] in Ontario. Summit sells their insulin solely through vets--yours will need to place the order for you.

Summit's insulin is comparable to Insuvet Protamine Zinc, and the Hypurin Bovine Protamine Zinc insulin of CP Pharma.

There are also pharmacies in the US and UK that compound PZI based on human ("regular") or animal-source insulins. It is possible to have PZI Humulin insulin of any strength compounded at some local compounding pharmacies. [37]

This link [38] and this one [39] list some of those compounding pharmacies, their contact information, and prices for their insulins.

Importing-Canada Edit

Your vet may also be able to obtain manufactured PZI insulin for you through Health Canada's Emergency Drug Release program. [40] With it, you are able to receive up to 6 months worth of insulin; a C$ 50.00 fee for the application is required. [41] If permitted, you would then be eligible to import PZI insulins such as Hypurin Bovine Protamine Zinc, as well as the other insulins CP Pharma produces.

The program is similar to Health Canada's Special Access Programme [42] for importing necessary drugs for people.

ReferencesEdit

  1. Definition of Protamine Zinc Insulin. Merck Manual.
  2. Nelson, Richard (2006). Selecting an Insulin for Treatment of Diabetes Mellitus in Dogs & Cats-Page 40. OSU Endocrine Symposium.
  3. Ruchinsky, Renee, et. al. (2010). Diabetes Management Guidelines for Dogs and Cats-page 7. American Animal Hospital Association.
  4. Scott-Moncrieff, Catherine (2009). Canine and Feline Diabetes Mellitus I-page 4. Western Veterinary Conference.
  5. ProZinc FAQ's. Boehringer Ingelheim Animal Health.
  6. Gordon, Jana (April 2008). Insulin therapy: Past, present and future (Proceedings). DVM 360.
  7. The History of Insulin. Novo Nordisk. (page 14)
  8. Dumitriu, Severian (2001). Polymeric Biomaterials, Revised and Expanded 1104. CRC Press.
  9. Chase, Lillian A. (1938). Some Rules for Dosage of Protamine Zinc Insulin. Canadian Medical Journal.
  10. 10.0 10.1 10.2 Excess Protamine Prohibits Same-Syringe Mixing of Protamine Zinc Insulins. NHS.
  11. Harrower AD, Duncan LJ, Clarke BF. (1975). Comparison of Injection Techniques for Soluble and Protamine Zinc Insulins in Diabetes Mellitus. Practitioner.
  12. Petsulin Protamine Zinc Page 5-Incompatibilities. Dechra.
  13. 13.0 13.1 Merck Manual. Inject Protamine Zinc Insulin Separately-Excess Protamine.
  14. Greco, Deborah (2010). Treating Diabetes Mellitus in Dogs and Cats. Western Veterinary Conference.
  15. Williams, Robert (1968). PZI Insulin--More Protamine Than NPH/Isophane Insulin-Textbook of Endocrinology, 4th edition. W.B. Saunders.
  16. Proteolytic Enzymes. Wikipedia.
  17. DeRuiter, Jack. Excess Protamine in Protamine Zinc Insulin Formula. Auburn University.
  18. Harrower AD, Duncan LJ, Clarke BF. (1975). Comparison of Injection Techniques for Soluble and Protamine Zinc Insulins in Diabetes Mellitus. Practitioner.
  19. Petsulin Protamine Zinc Page 5 Incompatibilities. Dechra.
  20. ProZinc-not studied in dogs-ProZinc FAQ's. Boehringer Ingelheim Animal Health.
  21. British Pharmacoepia & United States Pharmacoepia Protamine Zinc Insulin Defined. InChem.
  22. Discontinuation of Insuvet Insulins. My Online Vet UK.
  23. Insuvet Discontinuation. VioVet UK.
  24. Pfizer insulin products currently unavailable. Veterinary News (29 October 2010).
  25. 25.0 25.1 25.2 SPAH Contracts CP/Wockhardt UK for Insuvet Insulins. Wockhardt.
  26. Hypurin Bovine Neutral. Wockhardt UK.
  27. Hypurin Bovine Lente. Wockhardt UK.
  28. Hypurin Bovine Protamine Zinc. Wockhardt UK.
  29. Hypurin Bovine Protamine Zinc. Wockhardt UK.
  30. ProZinc FAQ's. Boehringer Ingelheim Animal Health.
  31. BCP Veterinary Pharmacy Website.
  32. Sources of PZI in various countries. Feline Diabetes.
  33. Stokes' Veterinary Medicines Page. Stokes Pharmacy.
  34. Stokes Pork PZI. Stokes Pharmacy.
  35. Stokes Bovine PZI. Stokes Pharmacy.
  36. Summit Veterinary Pharmacy Website
  37. Pet Health: PZI (Protamine Zinc Insulin). Feline Diabetes.
  38. PZI Sources. Felinediabetes.com.
  39. PZI Source list. Petdiabetes.org.
  40. Veterinary: Emergency Drug Release Information. HealthCanada.
  41. Emergency Drug Release Form. HealthCanada.
  42. Special Access Programme. HealthCanada.

More InformationEdit


Related pages
91 main
Cp wockhardt bovine insulins
Cp wockhardt bovine insulins
Insuvet Protamine Zinc
Hypurin Bovine Protamine Zinc
Hypurin Vet Protamine Zinc

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