Using porcine zinc insulin suspension in the management of canine diabetes mellitus (Sponsored by Intervet/Schering-Plough Animal Health)

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May 01, 2008


Figure 1. Vetsulin (Intervet, a part of Schering-Plough)
Vetsulin (porcine insulin zinc suspension, Figure 1) is the first FDA-approved veterinary product indicated for the reduction of hyperglycemia and hyperglycemia-associated clinical signs in dogs with diabetes mellitus. It is registered in 24 other countries as Caninsulin and has been used since 1990.

Vetsulin is supplied as a sterile injectable suspension in multidose vials containing either 2.5 ml or 10 ml of 40 U/ml (U-40) porcine insulin zinc suspension. Vials are supplied in cartons of one 10-ml vial and cartons of 10 2.5-ml vials and should be kept refrigerated. It is recommended to replace opened vials on a monthly basis.

Pharmacokinetics


Figure 2. Peak activity of Vetsulin
Vetsulin is a sterile, aqueous suspension of purified porcine insulin. It contains 40 U/ml, consisting of 30% amorphous and 70% crystalline zinc insulin in a neutral buffer at a pH of 7.35. Vetsulin is a lente, or intermediate-acting, insulin. In dogs, the amorphous fraction has peak activity approximately four hours after subcutaneous administration, and its effects last for about eight hours. Thereafter, the effect is maintained by the crystalline fraction, which has a slower onset of action and peak effects around 11 hours following the injection (Figure 2). Afterward, the effect gradually declines to zero.

Vetsulin should not be diluted because the amount of soluble insulin is increased by the aqueous diluent used, which results in an alteration of the pharmacokinetics. With a larger aqueous fraction and smaller crystalline fraction, a decrease in the crystalline portion responsible for the second peak of insulin activity would occur.

As porcine insulin, Vetsulin has the same amino acid sequence as canine insulin. This may help decrease the risk of anti-insulin antibody development, which may interfere with the action of the insulin. In a recent study, the presence of anti-insulin antibodies was determined by ELISA in serum samples from 30 diabetic dogs receiving bovine insulin therapy and 30 normoglycemic dogs.1 Twenty of the diabetic dogs had significant reactivity to both bovine (heterologous) and porcine (homologous) insulin compared with control dogs. In contrast, researchers saw no significant difference between the two populations in reactivity to canine distemper virus or canine thyroglobulin. The high degree of correlation between anti-bovine insulin and anti-porcine insulin antibodies suggested cross-reactivity, which was confirmed by performing a competition ELISA, which showed antibody binding to bovine insulin inhibited by pre-incubating serum with porcine insulin.

These data suggest that treatment of diabetic dogs with bovine insulin could lead to anti-insulin antibody production. While anti-insulin antibodies should not develop in newly diagnosed diabetic dogs that are administered Vetsulin, it is possible that dogs initially treated with bovine insulin may have cross-reactivity with the porcine insulin product.