Pharmacokinetics and tolerability of intravenous infusion of adenosine (SUNY4001) in healthy volunteers.

Aims 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 µg 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 ≤ 140 µg kg−1 min−1 was concluded to be generally well tolerated.