PMID- 32423275
OWN - NLM
STAT- MEDLINE
DCOM- 20210723
LR  - 20210723
IS  - 1941-2703 (Electronic)
IS  - 1941-2711 (Print)
IS  - 1941-2711 (Linking)
VI  - 33
IP  - 5
DP  - 2020 Oct
TI  - Pharmacokinetic Study of Epinephrine Hydrofluoroalkane (Primatene MIST) 
      Metered-Dose Inhaler.
PG  - 282-287
LID - 10.1089/jamp.2019.1577 [doi]
AB  - Background: Primatene((R)) MIST CFC, an epinephrine metered-dose inhaler (MDI), was 
      discontinued from the market owing to environmental concerns from its use of 
      chlorofluorocarbon (CFC) propellant. As a result, a new epinephrine MDI was 
      developed using hydrofluoroalkane (HFA) propellant. This article reports the 
      pharmacokinetic (PK) profile of the newly Food and Drug Administration-approved 
      epinephrine HFA MDI. Methods: A randomized, evaluator-blinded, active-controlled, 
      single-dose, two-arm crossover study was conducted to evaluate the PK profile of 
      epinephrine HFA (Primatene((R)) MIST) and epinephrine CFC (Primatene((R)) MIST CFC) 
      in 23 healthy volunteers to characterize the epinephrine absorption extent and 
      rate. The study was performed at a high dose of five times the normal dose to 
      obtain measurable plasma epinephrine levels. Plasma epinephrine levels were 
      measured and safety was assessed by adverse events (AEs), vital signs, clinical 
      laboratory tests, and physical examinations. Results: Epinephrine HFA 
      demonstrated a greater systemic drug exposure (greater area under the curve) than 
      that of epinephrine CFC ( approximately 37% higher). The C(max) occurred at  approximately 2 minutes and was 
      significantly higher in the epinephrine HFA group (0.18 ng/mL) compared with the 
      CFC version (0.046 ng/mL) at normal dose. Within 20 minutes, both groups 
      demonstrated comparable plasma epinephrine levels. No clinically significant 
      adverse effects were found to be associated with epinephrine HFA, even after an 
      ultrahigh dose (i.e., 10 inhalations). Conclusions: The systemic exposure of 
      epinephrine HFA was found to be higher for the first 20 minutes, and then 
      comparable with epinephrine CFC. Minimal AEs were found in this study despite the 
      very high 1250-2200 mug inhaled doses (i.e., 10 inhalations) used for PK 
      characterization.
FAU - Kerwin, Edward M
AU  - Kerwin EM
AD  - Clinical Research Institute of Southern Oregon, Medford, Oregon, USA.
FAU - Marrs, Tony
AU  - Marrs T
AD  - Amphastar Pharmaceuticals, Inc., Rancho Cucamonga, California, USA.
FAU - Luo, Mary Z
AU  - Luo MZ
AD  - Amphastar Pharmaceuticals, Inc., Rancho Cucamonga, California, USA.
FAU - Zhang, Jack Y
AU  - Zhang JY
AD  - Amphastar Pharmaceuticals, Inc., Rancho Cucamonga, California, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01188577
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200518
PL  - United States
TA  - J Aerosol Med Pulm Drug Deliv
JT  - Journal of aerosol medicine and pulmonary drug delivery
JID - 101475057
RN  - 0 (Aerosol Propellants)
RN  - 0 (Bronchodilator Agents)
RN  - 0 (Chlorofluorocarbons)
RN  - 0 (Hydrocarbons, Fluorinated)
RN  - R40P36GDK6 (apaflurane)
RN  - YKH834O4BH (Epinephrine)
MH  - Administration, Inhalation
MH  - Adolescent
MH  - Adult
MH  - Aerosol Propellants/*chemistry
MH  - Area Under Curve
MH  - Bronchodilator Agents/*administration & dosage/adverse effects/pharmacokinetics
MH  - Chlorofluorocarbons/chemistry
MH  - Cross-Over Studies
MH  - Dose-Response Relationship, Drug
MH  - Epinephrine/*administration & dosage/adverse effects/pharmacokinetics
MH  - Female
MH  - Humans
MH  - Hydrocarbons, Fluorinated/*chemistry
MH  - Male
MH  - Metered Dose Inhalers
MH  - Single-Blind Method
MH  - Young Adult
PMC - PMC7526295
OTO - NOTNLM
OT  - asthma
OT  - high dose
OT  - inhaled epinephrine
OT  - pharmacokinetic
OT  - systemic exposure
COIS- Dr. E.M.K. served on advisory boards, speaker panels, consultants, or received 
      travel reimbursement from Novartis, AstraZeneca, Amphastar, Forest, Pearl, 
      Sunovion, Teva, Theravance, Mylan, GSK, Boehringer Ingelheim, and Cipla outside 
      the submitted work. Dr. J.Y.Z., Dr. M.Z.L. and T.M. are employees of Amphastar 
      Pharmaceuticals, Inc. at the time of study and article preparation.
EDAT- 2020/05/20 06:00
MHDA- 2021/07/24 06:00
PMCR- 2020/09/30
CRDT- 2020/05/20 06:00
PHST- 2020/05/20 06:00 [pubmed]
PHST- 2021/07/24 06:00 [medline]
PHST- 2020/05/20 06:00 [entrez]
PHST- 2020/09/30 00:00 [pmc-release]
AID - 10.1089/jamp.2019.1577 [pii]
AID - 10.1089/jamp.2019.1577 [doi]
PST - ppublish
SO  - J Aerosol Med Pulm Drug Deliv. 2020 Oct;33(5):282-287. doi: 
      10.1089/jamp.2019.1577. Epub 2020 May 18.