Universität zu Köln

Frechen, Sebastian, Suleiman, Ahmed Abbas, Sigaroudi, Ali Mohammad Nejad, Wachall, Bertil and Fuhr, Uwe (2015). Population pharmacokinetic and pharmacodynamic modeling of epinephrine administered using a mobile inhaler. Drug Metab. Pharmacokinet., 30 (6). S. 391 - 400. TOKYO: JAPANESE SOC STUDY XENOBIOTICS. ISSN 1880-0920

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Abstract

Inhaled epinephrine is a potential alternative to self-administered intramuscular epinephrine in imminent anaphylactic reactions. The objective was to develop a pharmacokinetic-pharmacodynamic model describing exposure and effects on heart rate of inhaled epinephrine. Data from a 4-phase cross-over clinical trial in 9 healthy volunteers including 0.3 mg intramuscular epinephrine, two doses of inhaled epinephrine (4 mg/mL solution administered during [mean] 18 and 25 min, respectively) using a mobile pocket inhaler, and an inhaled placebo were analyzed using mixed-effects modeling. Inhaled epinephrine was available almost immediately and more rapidly than via the intramuscular route (absorption half-live 29 min). Epinephrine plasma concentrations declined rapidly after terminating inhalation (elimination half-life 4.1 min) offering the option to stop exposure in case of adverse events. While the expected maximum concentration was higher for inhaled epinephrine, this was not associated with safety concerns due to only moderate additional hemodynamic effects compared to intramuscular administration. Bioavailability after inhalation (4.7%) was subject to high interindividual and inter-occasional variability highlighting that training of inhalation would be essential for patients. The proposed model suggests that the use of a highly concentrated epinephrine solution via inhalation may offer an effective treatment option in anaphylaxis, while efficacy in patients remains to be shown. Copyright (C) 2015, The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Frechen, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Suleiman, Ahmed Abbas UNSPECIFIED UNSPECIFIED UNSPECIFIED Sigaroudi, Ali Mohammad Nejad UNSPECIFIED UNSPECIFIED UNSPECIFIED Wachall, Bertil UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuhr, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-384729
DOI:	10.1016/j.dmpk.2015.08.002
Journal or Publication Title:	Drug Metab. Pharmacokinet.
Volume:	30
Number:	6
Page Range:	S. 391 - 400
Date:	2015
Publisher:	JAPANESE SOC STUDY XENOBIOTICS
Place of Publication:	TOKYO
ISSN:	1880-0920
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MIXED-EFFECT MODELS; SUBCUTANEOUS INJECTION; SYSTEMIC ABSORPTION; ANAPHYLAXIS; ADRENALINE; INHALATION; NONMEM; QUANTIFICATION; CHILDREN; AEROSOL Multiple languages Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38472