Pharmacokinetics and tolerability of intravenous infusion of adenosine (SUNY4001) in healthy volunteers.
OBJECTIVE
To examine the tolerability and disposition of i.v. adenosine (SUNY4001) in healthy male Japanese volunteers.


METHODS
SUNY4001 was infused i.v. for 6 min at 0 (placebo), 60, 100, 120 and 140 microg kg-1 min-1 in a dose-escalating manner in 30 healthy subjects. Adenosine and its metabolites were determined in the plasma and urine.


RESULTS
Only plasma hypoxanthine was increased from 3 min during until 5-10 min after SUNY4001 infusion at the higher rates without any significant dose-related changes in plasma adenosine, inosine, xanthine or uric acid, or in urinary adenosine and all metabolites compared with the placebo. There was a dose-related increase in the incidence of subjective symptoms such as heat sensation, flushed face, dyspnoea, chest discomfort, etc. Transient and self-subsiding episodes of second-degree atrioventricular block were found in two subjects each at the higher doses.


CONCLUSIONS
Adenosine infusion at < or = 140 microg kg-1 min-1 was concluded to be generally well tolerated.
Uematsu
T
T
Department of Pharmacology, Gifu University School of Medicine, Gifu 500-8705, Japan. uematsu@cc.gifu-u.ac.jp
Kozawa
O
O
Matsuno
H
H
Niwa
M
M
Yoshikoshi
H
H
Oh-uchi
M
M
Kohno
K
K
Nagashima
S
S
Kanamaru
M
M
D000241:Adenosine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000328:Adult; D001283:Atrioventricular Node / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D014665:Vasodilator Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D014665:Vasodilator Agents; D000241:Adenosine