Mechanism Of Action

Regadenoson is a low affinity agonist (K_i &symp; 1.3 µM) for the A_2A adenosine receptor, with at least 10- fold lower affinity for the A₁ adenosine receptor (K_i > 16.5 µM), and weak, if any, affinity for the A2B and A3 adenosine receptors. Activation of the A_2A adenosine receptor by regadenoson produces coronary vasodilation and increases coronary blood flow (CBF).

Pharmacodynamics

•Coronary Blood Flow

Lexiscan causes a rapid increase in CBF which is sustained for a short duration. In patients undergoing coronary catheterization, pulsed-wave Doppler ultrasonography was used to measure the average peak velocity (APV) of coronary blood flow before and up to 30 minutes after administration of regadenoson (0.4 mg, intravenously). Mean APV increased to greater than twice baseline by 30 seconds and decreased to less than twice the baseline level within 10 minutes.

Myocardial uptake of the radiopharmaceutical is proportional to CBF. Because Lexiscan increases blood flow in normal coronary arteries with little or no increase in stenotic arteries, Lexiscan causes relatively less uptake of the radiopharmaceutical in vascular territories supplied by stenotic arteries. MPI intensity after Lexiscan administration is therefore greater in areas perfused by normal relative to stenosed arteries.

Effect of Aminophylline

Aminophylline (100 mg, administered by slow iv injection over 60 seconds) injected 1 minute after 0.4 mg Lexiscan in subjects undergoing cardiac catheterization, was shown to shorten the duration of the coronary blood flow response to Lexiscan as measured by pulsed-wave Doppler ultrasonography [see OVERDOSE].

Effect of Caffeine

A placebo-controlled clinical study assessed the effects of oral caffeine (200 mg) on the regadenoson- induced increase in coronary flow reserve (CFR) using positron emission tomography (PET) with radiolabeled water. Healthy subjects took caffeine 200 mg orally or placebo approximately 2 hours prior to Lexiscan administration. Following Lexiscan administration, the median CFR in caffeinated subjects was 92% of the CFR in non-caffeinated subjects [see DRUG INTERACTIONS and Patient Counseling Information ].

• Hemodynamic Effects

In clinical studies, the majority of patients had an increase in heart rate and a decrease in blood pressure within 45 minutes after administration of Lexiscan. Maximum hemodynamic changes after Lexiscan and Adenoscan in Studies 1 and 2 are summarized in Table 3.

Table 3: Hemodynamic Effects in Studies 1 and 2

• Respiratory Effects

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