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SUMMARY

The absorption kinetics of porcine regular insulin following iv, im, and sc administration were evaluated in 10 dogs with alloxan-induced diabetes mellitus. Plasma immunoreactive insulin (iri) concentrations were evaluated immediately prior to and at 10, 20, 30, 45, 60, 90, 120, 180, and 240 minutes following iv administration; and immediately prior to and every 30 minutes for 2 hours and then every hour for 6 hours following im and sc administration of 0.55 U of porcine regular insulin/kg of body weight. Model-independent pharmacokinetic analysis was performed on each data set.

Plasma iri concentration declined rapidly after iv administration of regular insulin and then returned to baseline iri concentration by 3.2 ± 0.8 hours. The absorption kinetics following iv administration of regular insulin were similar to those found in earlier studies in healthy dogs and human beings.

The im and sc routes of regular insulin administration resulted in a pharmacologic concentration of iri at 30 minutes. The peak mean (± SD) plasma iri concentration was significantly (P < 0.05) greater following sc administratin than it was following im administration of regular insulin (263 ± 185 and 151 ± 71 IμU/ml, respectively). The time of the peak plasma iri concentration (68 ± 31 minutes and 60 ± 30 minutes) and the time to return to baseline plasma iri concentration (5.8 ± 1.2 hours and 5.8 ± 1.3 hours) were not significantly different following sc and im administration of regular insulin, respectively. The absorption kinetics following sc administration of regular insulin were similar to those found in earlier studies in healthy dogs and human beings. The absorption kinetics following im administration of regular insulin differed from those found in earlier studies and was similar to the absorption kinetics of regular insulin administered sc in this study. The reasons for this similarity were not readily apparent.

Free access
in American Journal of Veterinary Research

SUMMARY

Serum glucose and immunoreactive insulin concentrations were monitored after topical administration of an insulin-containing ophthalmic solution in 20 clinically normal cats. Three ophthalmic surface-acting agents, benzalkonium chloride, dimethyl sulfoxide, and proparacaine hydrochloride, were evaluated individually for their effectiveness in enhancing absorption of topically applied insulin. The ophthalmic effects of insulin-containing ophthalmic preparations were assessed by complete ophthalmic examination before and at the conclusion of each test period. Withholding of food overnight (12 hours) preceded each topical application of insulin-containing ophthalmic solution (12.25 to 26.4 U/cat), either alone or in combination with surface-acting agents, after which blood samples were drawn serially from an indwelling iv catheter over a period of 8 hours. Baseline serum insulin concentration, after food was withheld for 12 hours, in nonstressed cats was 6.0 μU/ml (geometric mean), and an exponentiation of the logarithmic quantity (mean ± sd) yielded values of 1.5 to 23.0 μU/ml. All ophthalmic solutions tested failed to significantly lower serum glucose concentration or increase serum insulin concentration. Solutions used did not induce deleterious effect on ocular structures. Results indicate that topical administration of insulin-containing ophthalmic solution, either alone at the concentrations used or in combination with surfaceacting agents, did not result in effective absorption of insulin across the conjunctival and lacrimal nasal mucosa in biologically relevent quantities. Thus, this route of insulin administration, under these specific conditions, is not an effective alternative or adjunct to SC administration of insulin for treatment of cats with insulin-dependent diabetes mellitus or severe noninsulin-dependent diabetes mellitus.

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in American Journal of Veterinary Research

Summary

The absorption kinetics and glycemic effects of 3 long-acting insulin preparations (protamine zinc beefpork insulin, ultralente beef-pork insulin, and ultralente human insulin) were evaluated in 9 healthy, adult, domestic shorthair cats (6 males, 3 females). A triple crossover study was performed, in which the serial serum concentrations of insulin and glucose were determined over a 24-hour period after SC administration of the 3 insulin preparations (dosage, 1.0 U/kg of body weight) at 3-week intervals. A control study was also performed in 4 of the cats by serially collecting samples for insulin and glucose determinations after administration of insulin diluent. After administration of protamine zinc insulin (pzi), mean (± sem) serum insulin concentration increased significantly (P < 0.05) above baseline, reached a peak value (484 ± 287 pmol/L) at 1 hour, and remained significantly (P < 0.05) higher than baseline at 24 hours. After administration of ultralente human insulin, the serum insulin curve was similar to that obtained after pzi administration, but mean serum insulin concentration took longer to peak (538 ± 177 pmol/L at 4 hours). After administration of ultralente beef-pork insulin, mean peak serum insulin concentration was lower (220 ± 54 pmol/L, not statistically significant) than that obtained after administration of pzi and ultralente human insulins; it then decreased to values statistically indistinguishable from baseline by 16 hours. The area under the serum insulin concentration curve for pzi (5,063 ±681 pmol • h/L) and ultralente human insulin (4,138 ± 439 pmol • h/L) was significantly (P < 0.05) larger than that for ultralente beef-pork insulin (2,378 ± 561 pmol • h/L). Serum glucose concentration decreased after administration of all 3 insulins, but the decrease was not different from that observed after diluent (control) administration. Results of this study indicate that differences may exist between absorption of pzi, ultralente human, and ultralente beef-pork insulins. Of the 2 ultralente insulin preparations, human insulin appears better absorbed than beef-pork insulin, but these findings need to be confirmed in cats with naturally acquired diabetes mellitus.

Free access
in American Journal of Veterinary Research

Metformin (1,1-dimethylbiguanide) is an orally administered antihyperglycemic drug used commonly for management of type 2 diabetes mellitus in humans ( Figure 1 ). 1,2 It is used to control blood glucose concentrations by inhibiting hepatic

Full access
in American Journal of Veterinary Research

. Type 2 diabetes mellitus with pancreatic B cell dysfunction in 3 horses confirmed with minimal model analysis . Equine Vet J 2009 ; 41 : 924 – 929 . 10.2746/042516409X452152 9 Johnson PJ

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in American Journal of Veterinary Research

Metformin (1,1-dimethylbiguanide) is a biguanide primarily used for the management of non–insulin-dependent diabetes mellitus in humans and is the recommended first-line treatment following diagnosis. 1 Metformin does not appear to affect

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in American Journal of Veterinary Research

contraindicated in cats with diabetes mellitus, infectious disease, and certain types of heart disease; therefore, alternative treatments should be explored. In humans, second-generation antihistamines, such as cetirizine, have provided relief to patients that had

Full access
in American Journal of Veterinary Research