Intranasal epinephrine effects on epinephrine pharmacokinetics and heart rate in a nasal congestion canine model
Abstract Background Histamine release and vasodilation during an allergic reaction can alter the pharmacokinetics of drugs administered via the intranasal (IN) route. The current study evaluated the effects of histamine-induced nasal congestion on epinephrine pharmacokinetics and heart rate changes...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12931-020-01343-x |
| _version_ | 1828399011796615168 |
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| author | Richard Tuttle Luca Popescu Scott Hill Amber Slanczka Jeffrey Jankowski Katherine Barre Erika Krueger Desmond Slade Claire Croutch Matthew Robben Zack Mesa Michael Mesa Kenneth L. Dretchen |
| author_facet | Richard Tuttle Luca Popescu Scott Hill Amber Slanczka Jeffrey Jankowski Katherine Barre Erika Krueger Desmond Slade Claire Croutch Matthew Robben Zack Mesa Michael Mesa Kenneth L. Dretchen |
| author_sort | Richard Tuttle |
| collection | DOAJ |
| description | Abstract Background Histamine release and vasodilation during an allergic reaction can alter the pharmacokinetics of drugs administered via the intranasal (IN) route. The current study evaluated the effects of histamine-induced nasal congestion on epinephrine pharmacokinetics and heart rate changes after IN epinephrine. Methods Dogs received 5% histamine or saline IN followed by 4 mg epinephrine IN. Nasal restriction pressure, epinephrine concentration, and heart rate were assessed. Maximum concentration (Cmax), area under plasma concentration-time curve from 1 to 90 min (AUC1–90), and time to reach Cmax (Tmax) were measured. Clinical observations were documented. Results In the 12 dogs in this study, nasal congestion occurred at 5–10 min after IN histamine administration versus no nasal congestion after IN saline. After administration of IN epinephrine, IN histamine-mediated nasal congestion was significantly reduced to baseline levels at 60, 80, and 100 min. There were no significant differences in Cmax and AUC1–90 between histamine and saline groups after IN epinephrine delivery (3.5 vs 1.7 ng/mL, p = 0.06, and 117 vs 59 ng/mL*minutes, p = 0.09, respectively). After receiving IN epinephrine, the histamine group had a significantly lower Tmax versus the saline group (6 vs 70 min, respectively; p = 0.02). Following IN epinephrine administration, the histamine group showed rapidly increased heart rate at 5 min, while there was a delayed increase in heart rate (occurring 30–60 min after administration) in the saline group. Clinical observations included salivation and emesis. Conclusion IN histamine led to more rapid epinephrine absorption and immediately increased heart rate compared with IN saline. IN epinephrine decreased histamine-induced nasal congestion. |
| first_indexed | 2024-12-10T09:10:35Z |
| format | Article |
| id | doaj.art-346e71df9ee640aba0214967e6a3534e |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-12-10T09:10:35Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-346e71df9ee640aba0214967e6a3534e2022-12-22T01:55:01ZengBMCRespiratory Research1465-993X2020-04-012111710.1186/s12931-020-01343-xIntranasal epinephrine effects on epinephrine pharmacokinetics and heart rate in a nasal congestion canine modelRichard Tuttle0Luca Popescu1Scott Hill2Amber Slanczka3Jeffrey Jankowski4Katherine Barre5Erika Krueger6Desmond Slade7Claire Croutch8Matthew Robben9Zack Mesa10Michael Mesa11Kenneth L. Dretchen12MRIGlobalMRIGlobalMRIGlobalCharles River Laboratories, IncCharles River Laboratories, IncMRIGlobalMRIGlobalMRIGlobalMRIGlobalRobben Consulting, LLCMesa Science Associates, IncMesa Science Associates, IncMesa Science Associates, IncAbstract Background Histamine release and vasodilation during an allergic reaction can alter the pharmacokinetics of drugs administered via the intranasal (IN) route. The current study evaluated the effects of histamine-induced nasal congestion on epinephrine pharmacokinetics and heart rate changes after IN epinephrine. Methods Dogs received 5% histamine or saline IN followed by 4 mg epinephrine IN. Nasal restriction pressure, epinephrine concentration, and heart rate were assessed. Maximum concentration (Cmax), area under plasma concentration-time curve from 1 to 90 min (AUC1–90), and time to reach Cmax (Tmax) were measured. Clinical observations were documented. Results In the 12 dogs in this study, nasal congestion occurred at 5–10 min after IN histamine administration versus no nasal congestion after IN saline. After administration of IN epinephrine, IN histamine-mediated nasal congestion was significantly reduced to baseline levels at 60, 80, and 100 min. There were no significant differences in Cmax and AUC1–90 between histamine and saline groups after IN epinephrine delivery (3.5 vs 1.7 ng/mL, p = 0.06, and 117 vs 59 ng/mL*minutes, p = 0.09, respectively). After receiving IN epinephrine, the histamine group had a significantly lower Tmax versus the saline group (6 vs 70 min, respectively; p = 0.02). Following IN epinephrine administration, the histamine group showed rapidly increased heart rate at 5 min, while there was a delayed increase in heart rate (occurring 30–60 min after administration) in the saline group. Clinical observations included salivation and emesis. Conclusion IN histamine led to more rapid epinephrine absorption and immediately increased heart rate compared with IN saline. IN epinephrine decreased histamine-induced nasal congestion.http://link.springer.com/article/10.1186/s12931-020-01343-xEpinephrineNasal congestionHistamineVasodilationIntranasalSevere allergy |
| spellingShingle | Richard Tuttle Luca Popescu Scott Hill Amber Slanczka Jeffrey Jankowski Katherine Barre Erika Krueger Desmond Slade Claire Croutch Matthew Robben Zack Mesa Michael Mesa Kenneth L. Dretchen Intranasal epinephrine effects on epinephrine pharmacokinetics and heart rate in a nasal congestion canine model Respiratory Research Epinephrine Nasal congestion Histamine Vasodilation Intranasal Severe allergy |
| title | Intranasal epinephrine effects on epinephrine pharmacokinetics and heart rate in a nasal congestion canine model |
| title_full | Intranasal epinephrine effects on epinephrine pharmacokinetics and heart rate in a nasal congestion canine model |
| title_fullStr | Intranasal epinephrine effects on epinephrine pharmacokinetics and heart rate in a nasal congestion canine model |
| title_full_unstemmed | Intranasal epinephrine effects on epinephrine pharmacokinetics and heart rate in a nasal congestion canine model |
| title_short | Intranasal epinephrine effects on epinephrine pharmacokinetics and heart rate in a nasal congestion canine model |
| title_sort | intranasal epinephrine effects on epinephrine pharmacokinetics and heart rate in a nasal congestion canine model |
| topic | Epinephrine Nasal congestion Histamine Vasodilation Intranasal Severe allergy |
| url | http://link.springer.com/article/10.1186/s12931-020-01343-x |
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