Pharmacokinetics and safety of binodenoson after intravenous dose escalation in healthy volunteers.
BACKGROUND
Binodenoson, a highly selective agonist of the adenosine A 2A receptor, is being developed as a short-acting coronary vasodilator as an adjunct to radiotracers for use in myocardial stress imaging. This study was designed to assess the single-dose pharmacokinetics, safety, and tolerability of intravenous binodenoson.


RESULTS
This was a single-center, open-label, nonrandomized, dose-escalation study in 24 healthy volunteers. Each subject received 3 successive intravenous doses of binodenoson (0.1, 0.2, 0.4, 0.6, 1, 2, 3, 4, 5, and 6 microg/kg), each infused over a period of 10 minutes and separated by washout periods of at least 120 minutes. Generally, binodenoson was well tolerated. There were no serious adverse events. However, there was a dose-related increase in adverse events (e.g., headache, nausea, vasodilation, chest pain), consistent with the pharmacology of the drug. Binodenoson exhibited linear pharmacokinetics as indicated by a dose-proportional increase in peak concentration (C max ) and area under the concentration-time curve (AUC). Systemic clearance was independent of dose but was correlated with body weight. The mean terminal half-life of binodenoson across all doses was 10 +/- 4 minutes.


CONCLUSIONS
Overall, binodenoson was well tolerated and exhibited linear pharmacokinetics when administered intravenously over a 60-fold dose range from 0.1 to 6 microg/kg.
Barrett
Richard J
RJ
King Pharmaceuticals Research & Development Inc., 400 CentreGreen Way, Cary, NC 27513, USA.
Lamson
Michael J
MJ
Johnson
James
J
Smith
William B
WB
D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012016:Reference Values; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors
D019275:Radiopharmaceuticals; D000241:Adenosine; C101949:binodenoson