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Clinical pharmacokinetics of AZD3199, an inhaled ultra-long-acting β2-adrenoreceptor agonist (uLABA)
- Source :
- Drug Design, Development and Therapy, Vol 2015, Iss default, Pp 753-762 (2015)
- Publication Year :
- 2015
- Publisher :
- Dove Medical Press, 2015.
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Abstract
- Leif Bjermer,1 Piotr Kuna,2 Carin Jorup,3 Thomas Bengtsson,4 Johan Rosenborg4 1Department of Respiratory Medicine and Allergology, University Hospital, Lund, Sweden; 2Department of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland; 3AstraZeneca R&D, Mölndal, Sweden; 4StatMind, Lund, Sweden Objective: The clinical pharmacokinetics of AZD3199, an ultra-long-acting β2-agonist, were investigated in healthy volunteers and patients with asthma or chronic obstructive pulmonary disease (COPD). Materials and methods: Five studies are presented: one single ascending dose study in healthy Caucasian males; two multiple ascending dose studies in healthy males, one in Caucasians and one in Japanese; a Phase IIA asthma study; and a Phase IIB COPD study. Subjects received AZD3199 via a Spira nebulizer (Turbuhaler; equivalent delivered doses 5–3200 µg) or Turbuhaler (single delivered doses of 120–1920 µg or repeated delivered once-daily doses 240–1,680 µg). AZD3199 pharmacokinetics were assessed using total plasma concentration and urinary excretion, and tolerability using adverse events, clinical laboratory tests, and physical examinations. Results: AZD3199 appeared rapidly in the systemic circulation following single and multiple dosing in healthy volunteers and patients (maximum plasma concentration within 30 minutes), with dose-proportional time-independent pharmacokinetics. Plasma exposure to unmetabolized drug was similar in healthy volunteers and patients with asthma, but relatively lower in patients with COPD. Estimated terminal half-life was up to 142 hours in healthy Caucasian males. AZD3199 was well tolerated and showed no or at most mild systemic effects. Conclusion: AZD3199 plasma exposure in healthy volunteers and patients suggested linear pharmacokinetics and a long half-life. Systemic availability was similar in healthy subjects and patients with asthma, but was lower in patients with COPD. These clinical trials suggest that AZD3199 is well-tolerated in healthy male volunteers and patients, with no safety concerns identified to preclude further evaluation. Keywords: AZD3199, uLABA, COPD, asthma, pharmacokinetics, tolerability
- Subjects :
- Therapeutics. Pharmacology
RM1-950
Subjects
Details
- Language :
- English
- ISSN :
- 11778881
- Volume :
- 2015
- Issue :
- default
- Database :
- Directory of Open Access Journals
- Journal :
- Drug Design, Development and Therapy
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.04046619160e4a75a29325812556d8fc
- Document Type :
- article