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Diabetes in Pets

PZI

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Various types of veterinary insulins are known as PZI, "Protamine Zinc Insulin" . 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. Veterinary PZI is a particularly good insulin type for cats. PZI is rarely used in dogs but is considered when other insulins are not effective[1].

NB:Animal-source insulins are becoming harder to make now, and PZIVet's recent discontinuation (see below) is likely the first in a tragic series that will make porcine and bovine-source insulins rare. We can hope that new GM insulins will shortly be introduced to make up the gap.In the meantime the alternatives include these other PZI insulins, and of course the human GM analogs Levemir and Lantus.


PZI itself was introduced in 1936; it was the first insulin having any type of suspension. 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[2] .

Felineinsulin8

Feline insulin compared to Bovine, Porcine and Human versions. Up to 4 amino acids differ. The closest match to feline is bovine with only one amino acid difference; the least close is human with four amino acid differences[3].

Use and HandlingEdit

Cats tend to do well on PZI insulins. A 2001 study by Dr. Richard Nelson[4][5] showed that 75% of previously treated hard-to-regulate cats did well with the insulin. He goes on to saythat most cats do require PZI twice daily. The other 25% of tested cats did not reach peak with PZI insulin until 9 hours + after injection; they would likely be able to use only one shot per day. As the study illustrates, absorption, peak and duration of PZI is variable.

According to the UK's National Health Service[6], 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[7][8][9].

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. The additional protamine in the suspension[10] must first be broken down by proteolytic enzymes AKA proteases[11], 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

Protamine Zinc PZI[12] insulin cannot be combined with other insulins, due to the amount of protamine in the insulin's formula[13][14].


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[15][16]:

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 (except ProZinc) have a shelf life of three years (unopened).

ProZinc™Edit

Prozinc

ProZinc™ BIV's U-40 recombinant human insulin

ProZinc™ (protamine zinc recombinant human insulin) isBoehringer Ingelheim Vetmedica's replacement for PZI Vet insulin.  Boehringer Ingelheim Vetmedica was the purchaser of the PZI Vet franchise from IDEXX.  ProZinc is a manufactured (not compounded) U-40 insulin with FDA approval for use in diabetic cats.  Dosing is expected to be similar to PZI Vet insulin.  According to a BIV technical representative, during efficacy trials cats were switched from PZI Vet insulin to ProZinc in a 1:1 dosing ratio and they did "well."  It comes in 10ml bottles and has a shelf life of two years from the date of manufacture.  Like other insulins it must be kept refrigerated.  Generally ProZinc should be given twice a day.  It's characteristics (onset, peak, duration etc.) should approximate if not mirror the old PZI Vet insulin.  Since this is a new insulin [Nov 2010] and the supply is on "allocation," supplies may be limited during the immediate future.  It is available online, though some vets and some pharmacies.

PZI Vet (IDEXX) Edit

25934-1

PZI Vet by IDEXX-a U40, 90% beef, 10% pork protamine zinc insulin.

PZI Vet was made by IDEXX Laboratories (formerly Blue Ridge). PZI Vet is a

beef/pork PZI insulin commonly used in diabetic cats in the U.S. Some compounding pharmacies may refer to their PZI insulins as PZI Vet, but you aren't using PZI Vet.[17] unless it is made by IDEXX Labs. Unlike the other PZI's below, PZI Vet is a mix of beef and pork insulin. Beef insulin is closest to a cat's own insulin, and pork is identical to a dog's. PZI Vet is a manufactured insulin; the formula is that of Lilly's 90% beef/ 10% pork Iletin I Protamine Zinc insulin; Blue Ridge purchased it from Eli Lilly after the firm discontinued it.

Note: IDEXX PZI is being discontinued shortly due to animal insulin supply problems:

April 8, 2008

Dear Concerned Cat Owner,

Recently there have been some developments regarding the availability of PZI VET® (protamine zinc 
insulin), and I wanted to update you on the situation because it may impact your diabetic cat. You
may know that PZI VET is derived from bovine and porcine pancreatic glands, and unfortunately, the 
supply of our original raw material has been exhausted. As there are no FDA approved facilities for
harvesting bovine pancreatic tissue, we have determined after extensive study that further 
production of animal source insulins is not practical in a modern manufacturing environment.

Therefore, following the sale of our existing inventory, IDEXX will no longer manufacture or sell 
any animal-based insulin. We are currently in the process of notifying veterinarians who prescribe 
PZI-VET of the situation. As of April 1, 2008, there was a considerable inventory in distribution,
so please consult with your own veterinarian on the best course of action for your cat.


We appreciate that feline diabetes is a chronic condition requiring ongoing treatment and 
monitoring.
Accordingly, IDEXX remains committed to the treatment of this disease. We are working diligently to
develop and bring to market a new insulin product for the treatment of diabetes in cats.

Sincerely,


Cynthia Cole DVM, PhD, DACVCP
Manager, Professional Services Group
IDEXX Pharmaceuticals, Inc.

Insuvet PZI Edit

91 main

Insuvet Protamine Zinc--pure beef U100 PZI insulin.

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

Schering-Plough Animal Health contracted CP Pharma to produce its Insuvet line of bovine insulins[18]. The Insuvet line was sold to Pfizer Animal Health and it is believed that Pfizer continues to contract CP/Wockhardt UK for their production. Some UK pet pharmacies offer both the Insuvet-branded and the Hypurin-branded insulins. The only difference here may be pricing.

Insuvet insulins are only available in the UK; the option for those in other countries is either importing from CP Pharma 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

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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 humans and can be imported into the US and other countries.

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

Those CP Pharma insulins are comparable to Insuvet Protamine Zinc, made 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[19]. After the Insuvet line was sold to Pfizer Animal Health, it's believed that Pfizer still contracts CP/Wockhardt UK for their production.

==Edit

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.

SVP PZIEdit

Specialty Veterinary Pharmacy in Houston, TX, USA, Compounds (40u and 100u) PZI insulin (pure BEEF)


www.svpmeds.com Phone 1-877-673-3705

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[20] in Houston, TX, USA, manufactures and is the sole source supplier for BCP PZI. BCP PZI is commonly used in diabetic cats in the U.S. BCP PZI is a compounded insulin. Now that other pharmacies are discontinuing their bovine insulin, BCP Veterinary Pharmacy will most likely be the sole producer of Pure Beef PZI insulin in the U.S.

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.[21]

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.

UK, Canada, and US-other compounded PZIs Edit

Those in Canada can obtain 100% beef compounded PZI in U100 strength from Summit Veterinary Pharmacy[22] 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 and Hypurin Vet Protamine Zinc insulins 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: this relatively inexpensive route has produced satisfactory results for some cats.[23]

This link[24] and this one[25] 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[26]. With it, you are able to receive up to 6 months worth of insulin; a C$ 50.00 fee for the application is required [27]. If permitted, you would then be eligible to import PZI insulins such as PZI Vet,Insuvet Protamine Zinc, Hypurin Vet Protamine Zinc, or Hypurin Bovine Protamine Zinc, as well as the other insulins Insuvet and CP Pharma produce.

The program is similar to Health Canada's Special Access Programme [28] for importing necessary drugs for people.


Further ReadingEdit

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