Epinephrine in Anaphylaxis: Preclinical Study of Pharmacokinetics after Sublingual Administration of Taste-Masked Tablets for Potential Pediatric Use
<p dir="ltr">Epinephrine is a life-saving treatment in anaphylaxis. In community settings, a first-aid dose of epinephrine is injected from an auto-injector (EAI). Needle phobia highly contributes to EAI underuse, leading to fatalities—especially in children. A novel rapidly-disinteg...
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2018
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| _version_ | 1864513526387703808 |
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| author | Ousama Rachid (14158917) |
| author2 | Mutasem Rawas-Qalaji (18059995) Keith Simons (18059998) |
| author2_role | author author |
| author_facet | Ousama Rachid (14158917) Mutasem Rawas-Qalaji (18059995) Keith Simons (18059998) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ousama Rachid (14158917) Mutasem Rawas-Qalaji (18059995) Keith Simons (18059998) |
| dc.date.none.fl_str_mv | 2018-02-11T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/pharmaceutics10010024 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Epinephrine_in_Anaphylaxis_Preclinical_Study_of_Pharmacokinetics_after_Sublingual_Administration_of_Taste-Masked_Tablets_for_Potential_Pediatric_Use/25294897 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Pharmacology and pharmaceutical sciences bioavailability bioequivalence intramuscular auto-injector sublingual delivery rapidly-disintegrating tablets allergy anaphylaxis adrenaline epinephrine |
| dc.title.none.fl_str_mv | Epinephrine in Anaphylaxis: Preclinical Study of Pharmacokinetics after Sublingual Administration of Taste-Masked Tablets for Potential Pediatric Use |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Epinephrine is a life-saving treatment in anaphylaxis. In community settings, a first-aid dose of epinephrine is injected from an auto-injector (EAI). Needle phobia highly contributes to EAI underuse, leading to fatalities—especially in children. A novel rapidly-disintegrating sublingual tablet (RDST) of epinephrine was developed in our laboratory as a potential alternative dosage form. The aim of this study was to evaluate the sublingual bioavailability of epinephrine 30 mg as a potential pediatric dose incorporated in our novel taste-masked RDST in comparison with intramuscular (IM) epinephrine 0.15 mg from EAI, the recommended and only available dosage form for children in community settings. We studied the rate and extent of epinephrine absorption in our validated rabbit model (<i>n</i> = 5) using a cross-over design. The positive control was IM epinephrine 0.15 mg from an EpiPen Jr<sup>®</sup>. The negative control was a placebo RDST. Tablets were placed under the tongue for 2 min. Blood samples were collected at frequent intervals and epinephrine concentrations were measured using HPLC with electrochemical detection. The mean ± SEM maximum plasma concentration (<i>C</i><sub>max</sub>) of 16.7 ± 1.9 ng/mL at peak time (<i>T</i><sub>max</sub>) of 21 min after sublingual epinephrine 30 mg did not differ significantly (<i>p</i> > 0.05) from the <i>C</i><sub>max</sub> of 18.8 ± 1.9 ng/mL at a <i>T</i><sub>max</sub> of 36 min after IM epinephrine 0.15 mg. The <i>C</i><sub>max</sub> of both doses was significantly higher than the <i>C</i><sub>max</sub> of 7.5 ± 1.7 ng/mL of endogenous epinephrine after placebo. These taste-masked RDSTs containing a 30 mg dose of epinephrine have the potential to be used as an easy-to-carry, palatable, non-invasive treatment for anaphylactic episodes for children in community settings.</p><h2>Other Information</h2><p dir="ltr">Published in: Pharmaceutics<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/pharmaceutics10010024" target="_blank">https://dx.doi.org/10.3390/pharmaceutics10010024</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_25805dbf49392206c7ad6341d97c5ab7 |
| identifier_str_mv | 10.3390/pharmaceutics10010024 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25294897 |
| publishDate | 2018 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Epinephrine in Anaphylaxis: Preclinical Study of Pharmacokinetics after Sublingual Administration of Taste-Masked Tablets for Potential Pediatric UseOusama Rachid (14158917)Mutasem Rawas-Qalaji (18059995)Keith Simons (18059998)Biomedical and clinical sciencesPharmacology and pharmaceutical sciencesbioavailabilitybioequivalenceintramuscularauto-injectorsublingual deliveryrapidly-disintegratingtabletsallergyanaphylaxisadrenalineepinephrine<p dir="ltr">Epinephrine is a life-saving treatment in anaphylaxis. In community settings, a first-aid dose of epinephrine is injected from an auto-injector (EAI). Needle phobia highly contributes to EAI underuse, leading to fatalities—especially in children. A novel rapidly-disintegrating sublingual tablet (RDST) of epinephrine was developed in our laboratory as a potential alternative dosage form. The aim of this study was to evaluate the sublingual bioavailability of epinephrine 30 mg as a potential pediatric dose incorporated in our novel taste-masked RDST in comparison with intramuscular (IM) epinephrine 0.15 mg from EAI, the recommended and only available dosage form for children in community settings. We studied the rate and extent of epinephrine absorption in our validated rabbit model (<i>n</i> = 5) using a cross-over design. The positive control was IM epinephrine 0.15 mg from an EpiPen Jr<sup>®</sup>. The negative control was a placebo RDST. Tablets were placed under the tongue for 2 min. Blood samples were collected at frequent intervals and epinephrine concentrations were measured using HPLC with electrochemical detection. The mean ± SEM maximum plasma concentration (<i>C</i><sub>max</sub>) of 16.7 ± 1.9 ng/mL at peak time (<i>T</i><sub>max</sub>) of 21 min after sublingual epinephrine 30 mg did not differ significantly (<i>p</i> > 0.05) from the <i>C</i><sub>max</sub> of 18.8 ± 1.9 ng/mL at a <i>T</i><sub>max</sub> of 36 min after IM epinephrine 0.15 mg. The <i>C</i><sub>max</sub> of both doses was significantly higher than the <i>C</i><sub>max</sub> of 7.5 ± 1.7 ng/mL of endogenous epinephrine after placebo. These taste-masked RDSTs containing a 30 mg dose of epinephrine have the potential to be used as an easy-to-carry, palatable, non-invasive treatment for anaphylactic episodes for children in community settings.</p><h2>Other Information</h2><p dir="ltr">Published in: Pharmaceutics<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/pharmaceutics10010024" target="_blank">https://dx.doi.org/10.3390/pharmaceutics10010024</a></p>2018-02-11T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/pharmaceutics10010024https://figshare.com/articles/journal_contribution/Epinephrine_in_Anaphylaxis_Preclinical_Study_of_Pharmacokinetics_after_Sublingual_Administration_of_Taste-Masked_Tablets_for_Potential_Pediatric_Use/25294897CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/252948972018-02-11T03:00:00Z |
| spellingShingle | Epinephrine in Anaphylaxis: Preclinical Study of Pharmacokinetics after Sublingual Administration of Taste-Masked Tablets for Potential Pediatric Use Ousama Rachid (14158917) Biomedical and clinical sciences Pharmacology and pharmaceutical sciences bioavailability bioequivalence intramuscular auto-injector sublingual delivery rapidly-disintegrating tablets allergy anaphylaxis adrenaline epinephrine |
| status_str | publishedVersion |
| title | Epinephrine in Anaphylaxis: Preclinical Study of Pharmacokinetics after Sublingual Administration of Taste-Masked Tablets for Potential Pediatric Use |
| title_full | Epinephrine in Anaphylaxis: Preclinical Study of Pharmacokinetics after Sublingual Administration of Taste-Masked Tablets for Potential Pediatric Use |
| title_fullStr | Epinephrine in Anaphylaxis: Preclinical Study of Pharmacokinetics after Sublingual Administration of Taste-Masked Tablets for Potential Pediatric Use |
| title_full_unstemmed | Epinephrine in Anaphylaxis: Preclinical Study of Pharmacokinetics after Sublingual Administration of Taste-Masked Tablets for Potential Pediatric Use |
| title_short | Epinephrine in Anaphylaxis: Preclinical Study of Pharmacokinetics after Sublingual Administration of Taste-Masked Tablets for Potential Pediatric Use |
| title_sort | Epinephrine in Anaphylaxis: Preclinical Study of Pharmacokinetics after Sublingual Administration of Taste-Masked Tablets for Potential Pediatric Use |
| topic | Biomedical and clinical sciences Pharmacology and pharmaceutical sciences bioavailability bioequivalence intramuscular auto-injector sublingual delivery rapidly-disintegrating tablets allergy anaphylaxis adrenaline epinephrine |