Pharmacokinetic Study of Epinephrine Hydrofluoroalkane (Primatene MIST) Metered-Dose Inhaler
| Autor: | Tony Marrs, Jack Y Zhang, Edward Kerwin, Mary Z. Luo |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Pulmonary and Respiratory Medicine Adolescent Epinephrine Hydrocarbons Fluorinated Cmax Pharmaceutical Science Young Adult chemistry.chemical_compound Pharmacokinetics high dose Administration Inhalation medicine Humans Single-Blind Method Pharmacology (medical) Metered Dose Inhalers pharmacokinetic Original Research systemic exposure inhaled epinephrine Cross-Over Studies Chlorofluorocarbon Dose-Response Relationship Drug business.industry Inhaler Area under the curve asthma Crossover study Metered-dose inhaler Bronchodilator Agents Aerosol Propellants chemistry Area Under Curve Anesthesia Female Chlorofluorocarbons business medicine.drug |
| Zdroj: | Journal of Aerosol Medicine and Pulmonary Drug Delivery |
| ISSN: | 1941-2703 1941-2711 |
| Popis: | Background: Primatene® 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® MIST) and epinephrine CFC (Primatene® 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 (∼37% higher). The Cmax occurred at ∼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 μg inhaled doses (i.e., 10 inhalations) used for PK characterization. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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