title: Safety and tolerability of intravenous regadenoson in healthy subjects: A randomized, repeat-dose, placebo-controlled study.
abstract: Regadenoson is a selective A2Aadenosine receptor agonist indicated for radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress. However, the safety, tolerability, and plasma concentrations associated with repeated doses have not previously been assessed.
  
  
  
  Healthy males and females were randomized to receive intravenous regadenoson [100 μg (3 doses), 200 μg (3 doses), or 400 μg (2 doses)], or placebo (2 or 3 doses; 0.9% sodium chloride); all doses 10 minutes apart. The primary endpoint was vital sign measurements (blood pressure and heart rate). Secondary endpoints included 12-lead electrocardiogram measurements, clinical laboratory evaluations (hematology, chemistry, and urinalysis), and adverse events. Thirty-six subjects were randomized and completed the study. Plasma concentrations of regadenoson increased in a dose-related manner and with successive doses. No consistent effect was observed for systolic blood pressure, although diastolic blood pressure was slightly lower than placebo for all regadenoson groups. Transient, dose-dependent increases in heart rate were observed in all regadenoson groups. There were no serious adverse events; 27 adverse events occurred in 14 regadenoson-treated subjects vs two events in two placebo-treated subjects.
  
  
  
  Repeated doses of regadenoson appeared to be safe and well tolerated in healthy subjects.
authors.affiliation: Astellas Pharma Global Development, Inc., 1 Astellas Way, Northbrook, IL, 60062, USA. Robert.Townsend@astellas.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Townsend
authors.affiliation: Astellas Pharma Global Development, Inc., 1 Astellas Way, Northbrook, IL, 60062, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Desai
authors.affiliation: Randstad Pharma, Deerfield, IL, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Rammelsberg
authors.affiliation: Astellas Pharma Global Development, Inc., 1 Astellas Way, Northbrook, IL, 60062, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Kowalski
authors.affiliation: Astellas Research Institute of America, Bioanalysis-US, Skokie, IL, USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Simmons
authors.affiliation: Astellas Pharma Global Development, Inc., 1 Astellas Way, Northbrook, IL, 60062, USA.
authors.forename: Therese M
authors.initials: TM
authors.lastname: Kitt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis* / Q000209:etiology*; D005080:Exercise Test / Q000009:adverse effects* / Q000379:methods*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D055414:Myocardial Perfusion Imaging; D015990:Placebo Effect; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects*; D012016:Reference Values; D018570:Risk Assessment; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D011687:Purines; D011720:Pyrazoles; D014665:Vasodilator Agents; C430916:regadenoson
keywords: Myocardial perfusion imaging; regadenoson; repeated doses; safety; tolerability