Intravenous adenosine substantially enhances myocardial salvage in experimental models of coronary reperfusion. Since adenosine may be potentially useful in settings where tissue-type plasminogen activator (t-PA) is employed, it would be important to assess its effect on t-PA clearance prior to initiating clinical studies. The hemodynamic and pharmacokinetic effects of a 150-minute infusions of adenosine (35 and 70 μg/kg/min) or vehicle (normal saline) in conjunction with a 60-minute infusion of t-PA were examined in six healthy male volunteers. High-dose adenosine produced a small but significant increase in heart rate and systolic blood pressure without changing diastolic pressure. Steady-state plasma levels of t-PA were achieved within 30 minutes of its infusion. t-PA clearance conformed to a two- compartment model with a t( 1/2 )α of 3.4±0.5 and a t( 1/2 )β of 29.1±6.2 and was unchanged after both doses of adenosine (30 μg/kg/min: 5.5±0.8 and 31.1±9.2; 70 μg/kg/min: 4.3±1.0 and 32.4±5.9, respectively; P = not significant vs saline). Fibrin autography demonstrated that plasma t-PA was largely in the free, active form with only a minor degree of complex formation. Adenosine had no effect on the disposition of t-PA in plasma. t-PA clearance displays linear pharmacokinetics, which allows extrapolation of our results to therapeutic doses in humans. Prolonged infusions of adenosine in doses that improve myocardial salvage in vivo do not alter the pharmacokinetics of t-PA in humans.
|Original language||English (US)|
|Number of pages||7|
|Journal||Coronary artery disease|
|State||Published - Dec 1 1991|
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine