Comparison of pharmacodynamics and pharmacokinetics of insulin degludec and insulin glargine 300 U/mL in healthy cats
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.domaniend.2019.04.001 http://hdl.handle.net/11449/189358 |
Resumo: | Insulin glargine 300 U/mL (IGla-U300) and insulin degludec (IDeg) are synthetic insulin analogs designed as basal insulin formulations. In people, IGla-U300 is more predictable and longer acting compared with glargine 100 U/mL. The duration of action of IDeg in people is > 42 h, allowing flexibility in daily administration. We hypothesized that IDeg would have longer duration of action compared with IGla-U300 in healthy purpose-bred cats. Seven cats received 0.4 U/kg (subcutaneous) of IDeg and IGla-U300 on two different days, >1 wk apart. Exogenous insulin was measured and pharmacodynamic parameters were derived from glucose infusion rates during isoglycemic clamps and suppression of endogenous insulin. The Shapiro-Wilk test was used to assess normality, and normally distributed parameters were compared using paired t-tests. There was no difference between IDeg and IGla-U300 in onset, peak action, or total metabolic effect. On average, time to peak action (TPEAK) of IGla-U300 was 145 ± 114 min (95% confidence interval [CI] = 25–264) longer than TPEAK of IDeg (P = 0.03) and duration of action (TDUR) of IGla-U300 was 250 ± 173 min (95% CI = 68–432) longer than TDUR of IDeg (P = 0.02). The “flatness” of the time-action profile (as represented by the quotient of peak action/TDUR) was significantly greater for IGla-U300 compared with IDeg (P = 0.04). Overall, insulin concentration measurements concurred with findings from isoglycemic clamps. Based on these data, IDeg is not suitable for once-daily administration in cats. The efficacy of once-daily IGla-U300 in diabetic cats should be further investigated. |
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Comparison of pharmacodynamics and pharmacokinetics of insulin degludec and insulin glargine 300 U/mL in healthy catsDiabetes mellitusIsoglycemic clampInsulin glargine 300 U/mL (IGla-U300) and insulin degludec (IDeg) are synthetic insulin analogs designed as basal insulin formulations. In people, IGla-U300 is more predictable and longer acting compared with glargine 100 U/mL. The duration of action of IDeg in people is > 42 h, allowing flexibility in daily administration. We hypothesized that IDeg would have longer duration of action compared with IGla-U300 in healthy purpose-bred cats. Seven cats received 0.4 U/kg (subcutaneous) of IDeg and IGla-U300 on two different days, >1 wk apart. Exogenous insulin was measured and pharmacodynamic parameters were derived from glucose infusion rates during isoglycemic clamps and suppression of endogenous insulin. The Shapiro-Wilk test was used to assess normality, and normally distributed parameters were compared using paired t-tests. There was no difference between IDeg and IGla-U300 in onset, peak action, or total metabolic effect. On average, time to peak action (TPEAK) of IGla-U300 was 145 ± 114 min (95% confidence interval [CI] = 25–264) longer than TPEAK of IDeg (P = 0.03) and duration of action (TDUR) of IGla-U300 was 250 ± 173 min (95% CI = 68–432) longer than TDUR of IDeg (P = 0.02). The “flatness” of the time-action profile (as represented by the quotient of peak action/TDUR) was significantly greater for IGla-U300 compared with IDeg (P = 0.04). Overall, insulin concentration measurements concurred with findings from isoglycemic clamps. Based on these data, IDeg is not suitable for once-daily administration in cats. The efficacy of once-daily IGla-U300 in diabetic cats should be further investigated.Department of Veterinary Medicine and Epidemiology University of California Davis, 1 Shields AvenueDepartment of Veterinary Surgical and Radiological Sciences University of California Davis, 1 Shields AvenueDepartment of Veterinary Clinic and Surgery UNESP - Univ. Estadual Paulista Jaboticabal, Via de Acesso Prof. Paulo Donato Castellani, s/nSchool of Nursing and Health Professions University of San Francisco, 2130 Fulton StreetDepartment of Veterinary Clinic and Surgery UNESP - Univ. Estadual Paulista Jaboticabal, Via de Acesso Prof. Paulo Donato Castellani, s/nDavisUniversidade Estadual Paulista (Unesp)University of San FranciscoGilor, C.Culp, W.Ghandi, S.do Carmo Emidio e Silva, J. A. [UNESP]Ladhar, A.Hulsebosch, S.2019-10-06T16:38:08Z2019-10-06T16:38:08Z2019-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article19-29http://dx.doi.org/10.1016/j.domaniend.2019.04.001Domestic Animal Endocrinology, v. 69, p. 19-29.0739-7240http://hdl.handle.net/11449/18935810.1016/j.domaniend.2019.04.0012-s2.0-85068269000Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengDomestic Animal Endocrinologyinfo:eu-repo/semantics/openAccess2024-06-06T14:10:47Zoai:repositorio.unesp.br:11449/189358Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-06-06T14:10:47Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Comparison of pharmacodynamics and pharmacokinetics of insulin degludec and insulin glargine 300 U/mL in healthy cats |
title |
Comparison of pharmacodynamics and pharmacokinetics of insulin degludec and insulin glargine 300 U/mL in healthy cats |
spellingShingle |
Comparison of pharmacodynamics and pharmacokinetics of insulin degludec and insulin glargine 300 U/mL in healthy cats Gilor, C. Diabetes mellitus Isoglycemic clamp |
title_short |
Comparison of pharmacodynamics and pharmacokinetics of insulin degludec and insulin glargine 300 U/mL in healthy cats |
title_full |
Comparison of pharmacodynamics and pharmacokinetics of insulin degludec and insulin glargine 300 U/mL in healthy cats |
title_fullStr |
Comparison of pharmacodynamics and pharmacokinetics of insulin degludec and insulin glargine 300 U/mL in healthy cats |
title_full_unstemmed |
Comparison of pharmacodynamics and pharmacokinetics of insulin degludec and insulin glargine 300 U/mL in healthy cats |
title_sort |
Comparison of pharmacodynamics and pharmacokinetics of insulin degludec and insulin glargine 300 U/mL in healthy cats |
author |
Gilor, C. |
author_facet |
Gilor, C. Culp, W. Ghandi, S. do Carmo Emidio e Silva, J. A. [UNESP] Ladhar, A. Hulsebosch, S. |
author_role |
author |
author2 |
Culp, W. Ghandi, S. do Carmo Emidio e Silva, J. A. [UNESP] Ladhar, A. Hulsebosch, S. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Davis Universidade Estadual Paulista (Unesp) University of San Francisco |
dc.contributor.author.fl_str_mv |
Gilor, C. Culp, W. Ghandi, S. do Carmo Emidio e Silva, J. A. [UNESP] Ladhar, A. Hulsebosch, S. |
dc.subject.por.fl_str_mv |
Diabetes mellitus Isoglycemic clamp |
topic |
Diabetes mellitus Isoglycemic clamp |
description |
Insulin glargine 300 U/mL (IGla-U300) and insulin degludec (IDeg) are synthetic insulin analogs designed as basal insulin formulations. In people, IGla-U300 is more predictable and longer acting compared with glargine 100 U/mL. The duration of action of IDeg in people is > 42 h, allowing flexibility in daily administration. We hypothesized that IDeg would have longer duration of action compared with IGla-U300 in healthy purpose-bred cats. Seven cats received 0.4 U/kg (subcutaneous) of IDeg and IGla-U300 on two different days, >1 wk apart. Exogenous insulin was measured and pharmacodynamic parameters were derived from glucose infusion rates during isoglycemic clamps and suppression of endogenous insulin. The Shapiro-Wilk test was used to assess normality, and normally distributed parameters were compared using paired t-tests. There was no difference between IDeg and IGla-U300 in onset, peak action, or total metabolic effect. On average, time to peak action (TPEAK) of IGla-U300 was 145 ± 114 min (95% confidence interval [CI] = 25–264) longer than TPEAK of IDeg (P = 0.03) and duration of action (TDUR) of IGla-U300 was 250 ± 173 min (95% CI = 68–432) longer than TDUR of IDeg (P = 0.02). The “flatness” of the time-action profile (as represented by the quotient of peak action/TDUR) was significantly greater for IGla-U300 compared with IDeg (P = 0.04). Overall, insulin concentration measurements concurred with findings from isoglycemic clamps. Based on these data, IDeg is not suitable for once-daily administration in cats. The efficacy of once-daily IGla-U300 in diabetic cats should be further investigated. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-10-06T16:38:08Z 2019-10-06T16:38:08Z 2019-10-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.domaniend.2019.04.001 Domestic Animal Endocrinology, v. 69, p. 19-29. 0739-7240 http://hdl.handle.net/11449/189358 10.1016/j.domaniend.2019.04.001 2-s2.0-85068269000 |
url |
http://dx.doi.org/10.1016/j.domaniend.2019.04.001 http://hdl.handle.net/11449/189358 |
identifier_str_mv |
Domestic Animal Endocrinology, v. 69, p. 19-29. 0739-7240 10.1016/j.domaniend.2019.04.001 2-s2.0-85068269000 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Domestic Animal Endocrinology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
19-29 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1803650117240094720 |