Pharmacokinetics and pharmacodynamics of protamine zinc recombinant human insulin in healthy dogs

Clark, M., Thomaseth, K., Heit, M., Hoenig, M. Pharmacokinetics and pharmacodynamics of protamine zinc recombinant human insulin in healthy dogs. J. vet. Pharmacol. Therap. 35, 342–350. Protamine zinc insulins are generally considered to be long acting, with slow absorption from subcutaneous tissue....

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Veröffentlicht in:Journal of veterinary pharmacology and therapeutics 2012-08, Vol.35 (4), p.342-350
Hauptverfasser: CLARK, M, THOMASETH, K, HEIT, M, HOENIG, M
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THOMASETH, K
HEIT, M
HOENIG, M
description Clark, M., Thomaseth, K., Heit, M., Hoenig, M. Pharmacokinetics and pharmacodynamics of protamine zinc recombinant human insulin in healthy dogs. J. vet. Pharmacol. Therap. 35, 342–350. Protamine zinc insulins are generally considered to be long acting, with slow absorption from subcutaneous tissue. Protamine zinc recombinant human insulin (PZIR) may be useful to treat diabetic dogs. The purpose of this study was to describe the pharmacokinetics and pharmacodynamics of PZIR in dogs. PZIR was administered subcutaneously to 10 healthy Beagles using an incomplete crossover design, at doses of 0.3 or 0.5 U/kg (each n = 5), 0.8 U/kg (n = 10), or 0.8 U/kg at three separate sites (n = 6). Insulin and glucose concentrations were measured over 24 h. The shapes of insulin and glucose curves were variable among dogs, and the relationship between insulin dose, concentration, and glucose‐lowering effect was nonlinear. For single‐site 0.8 U/kg, median (range) onset of action was 3.5 h (0.5–10 h), time to glucose nadir was 14 h (5 to >24 h), and duration of action was >24 h (16 to >24 h). Mathematical model predictions of times to 50% and 90% insulin absorption, and fraction of insulin absorbed in 24 h, were not significantly different among protocols. Results confirm the tendency toward a late onset and long duration of action for PZIR in dogs. This insulin may be an alternative treatment option for diabetic dogs.
doi_str_mv 10.1111/j.1365-2885.2011.01329.x
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Pharmacokinetics and pharmacodynamics of protamine zinc recombinant human insulin in healthy dogs. J. vet. Pharmacol. Therap. 35, 342–350. Protamine zinc insulins are generally considered to be long acting, with slow absorption from subcutaneous tissue. Protamine zinc recombinant human insulin (PZIR) may be useful to treat diabetic dogs. The purpose of this study was to describe the pharmacokinetics and pharmacodynamics of PZIR in dogs. PZIR was administered subcutaneously to 10 healthy Beagles using an incomplete crossover design, at doses of 0.3 or 0.5 U/kg (each n = 5), 0.8 U/kg (n = 10), or 0.8 U/kg at three separate sites (n = 6). Insulin and glucose concentrations were measured over 24 h. The shapes of insulin and glucose curves were variable among dogs, and the relationship between insulin dose, concentration, and glucose‐lowering effect was nonlinear. For single‐site 0.8 U/kg, median (range) onset of action was 3.5 h (0.5–10 h), time to glucose nadir was 14 h (5 to &gt;24 h), and duration of action was &gt;24 h (16 to &gt;24 h). Mathematical model predictions of times to 50% and 90% insulin absorption, and fraction of insulin absorbed in 24 h, were not significantly different among protocols. Results confirm the tendency toward a late onset and long duration of action for PZIR in dogs. This insulin may be an alternative treatment option for diabetic dogs.</description><identifier>ISSN: 0140-7783</identifier><identifier>EISSN: 1365-2885</identifier><identifier>DOI: 10.1111/j.1365-2885.2011.01329.x</identifier><identifier>PMID: 22758791</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Absorption ; Animals ; Blood Glucose - metabolism ; dogs ; Dogs - blood ; Dogs - metabolism ; glucose ; Humans ; insulin ; Insulin - blood ; Insulin - metabolism ; Insulin, Isophane - metabolism ; Insulin, Isophane - pharmacokinetics ; Male ; mathematical models ; Models, Biological ; pharmacokinetics ; potassium ; Recombinant Proteins - metabolism ; Recombinant Proteins - pharmacokinetics ; zinc</subject><ispartof>Journal of veterinary pharmacology and therapeutics, 2012-08, Vol.35 (4), p.342-350</ispartof><rights>2011 Blackwell Publishing Ltd</rights><rights>2011 Blackwell Publishing Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4649-ddb2277c5297435bd9e6d686f9eccdfb4b475e47d93108d258be40e381eb6fcb3</citedby><cites>FETCH-LOGICAL-c4649-ddb2277c5297435bd9e6d686f9eccdfb4b475e47d93108d258be40e381eb6fcb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2885.2011.01329.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2885.2011.01329.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22758791$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CLARK, M</creatorcontrib><creatorcontrib>THOMASETH, K</creatorcontrib><creatorcontrib>HEIT, M</creatorcontrib><creatorcontrib>HOENIG, M</creatorcontrib><title>Pharmacokinetics and pharmacodynamics of protamine zinc recombinant human insulin in healthy dogs</title><title>Journal of veterinary pharmacology and therapeutics</title><addtitle>J Vet Pharmacol Ther</addtitle><description>Clark, M., Thomaseth, K., Heit, M., Hoenig, M. Pharmacokinetics and pharmacodynamics of protamine zinc recombinant human insulin in healthy dogs. J. vet. Pharmacol. Therap. 35, 342–350. Protamine zinc insulins are generally considered to be long acting, with slow absorption from subcutaneous tissue. Protamine zinc recombinant human insulin (PZIR) may be useful to treat diabetic dogs. The purpose of this study was to describe the pharmacokinetics and pharmacodynamics of PZIR in dogs. PZIR was administered subcutaneously to 10 healthy Beagles using an incomplete crossover design, at doses of 0.3 or 0.5 U/kg (each n = 5), 0.8 U/kg (n = 10), or 0.8 U/kg at three separate sites (n = 6). Insulin and glucose concentrations were measured over 24 h. The shapes of insulin and glucose curves were variable among dogs, and the relationship between insulin dose, concentration, and glucose‐lowering effect was nonlinear. For single‐site 0.8 U/kg, median (range) onset of action was 3.5 h (0.5–10 h), time to glucose nadir was 14 h (5 to &gt;24 h), and duration of action was &gt;24 h (16 to &gt;24 h). Mathematical model predictions of times to 50% and 90% insulin absorption, and fraction of insulin absorbed in 24 h, were not significantly different among protocols. Results confirm the tendency toward a late onset and long duration of action for PZIR in dogs. 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Pharmacokinetics and pharmacodynamics of protamine zinc recombinant human insulin in healthy dogs. J. vet. Pharmacol. Therap. 35, 342–350. Protamine zinc insulins are generally considered to be long acting, with slow absorption from subcutaneous tissue. Protamine zinc recombinant human insulin (PZIR) may be useful to treat diabetic dogs. The purpose of this study was to describe the pharmacokinetics and pharmacodynamics of PZIR in dogs. PZIR was administered subcutaneously to 10 healthy Beagles using an incomplete crossover design, at doses of 0.3 or 0.5 U/kg (each n = 5), 0.8 U/kg (n = 10), or 0.8 U/kg at three separate sites (n = 6). Insulin and glucose concentrations were measured over 24 h. The shapes of insulin and glucose curves were variable among dogs, and the relationship between insulin dose, concentration, and glucose‐lowering effect was nonlinear. For single‐site 0.8 U/kg, median (range) onset of action was 3.5 h (0.5–10 h), time to glucose nadir was 14 h (5 to &gt;24 h), and duration of action was &gt;24 h (16 to &gt;24 h). Mathematical model predictions of times to 50% and 90% insulin absorption, and fraction of insulin absorbed in 24 h, were not significantly different among protocols. Results confirm the tendency toward a late onset and long duration of action for PZIR in dogs. This insulin may be an alternative treatment option for diabetic dogs.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>22758791</pmid><doi>10.1111/j.1365-2885.2011.01329.x</doi><tpages>9</tpages></addata></record>
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subjects Absorption
Animals
Blood Glucose - metabolism
dogs
Dogs - blood
Dogs - metabolism
glucose
Humans
insulin
Insulin - blood
Insulin - metabolism
Insulin, Isophane - metabolism
Insulin, Isophane - pharmacokinetics
Male
mathematical models
Models, Biological
pharmacokinetics
potassium
Recombinant Proteins - metabolism
Recombinant Proteins - pharmacokinetics
zinc
title Pharmacokinetics and pharmacodynamics of protamine zinc recombinant human insulin in healthy dogs
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