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Dipyridamole Injection

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Dipyridamole Injection

CLINICAL PHARMACOLOGY

In a study of 10 patients with angiographically normal or minimally stenosed (less than 25% luminal diameter narrowing) coronary vessels, dipyridamole injection in a dose of 0.56 mg/kg infused over 4 minutes resulted in an average fivefold increase in coronary blood flow velocity compared to resting coronary flow velocity (range 3.8 to 7 times resting velocity). The mean time to peak flow velocity was 6.5 minutes from the start of the 4-minute infusion (range 2.5 to 8.7 minutes). Cardiovascular responses to the intravenous administration of dipyridamole when given to patients in the supine position include a mild but significant increase in heart rate of approximately 20% and mild but significant decreases in both systolic and diastolic blood pressure of approximately 2 to 8%, with vital signs returning to baseline values in approximately 30 minutes.

Mechanism of Action

Dipyridamole is a coronary vasodilator in man. The mechanism of vasodilation has not been fully elucidated, but may result from inhibition of uptake of adenosine, an important mediator of coronary vasodilation. The vasodilatory effects of dipyridamole are abolished by administration of the adenosine receptor antagonist theophylline.

How dipyridamole-induced vasodilation leads to abnormalities in thallium distribution and ventricular function is also uncertain but presumably represents a “steal” phenomenon in which relatively intact vessels dilate, and sustain enhanced flow, leaving reduced pressure and flow across areas of hemodynamically important coronary vascular constriction.

Pharmacokinetics and Metabolism

Plasma dipyridamole concentrations decline in a triexponential fashion following intravenous infusion of dipyridamole, with half-lives averaging 3 to 12 minutes, 33 to 62 minutes, and 11.6 to 15 hours. Two minutes following a 0.568 mg/kg dose of intravenous dipyridamole injection administered as a 4-minute infusion, the mean dipyridamole serum concentration is 4.6 ± 1.3 mcg/mL. The average plasma protein binding of dipyridamole is approximately 99%, primarily to a1-glycoprotein. Dipyridamole is metabolized in the liver to the glucuronic acid conjugate and excreted with the bile. The average total body clearance is 2.3 to 3.5 mL/min/kg, with an apparent volume of distribution at steady state of 1 to 2.5 L/kg and a central apparent volume of 3 to 5 liters.

Last reviewed on RxList: 3/4/2009
This monograph has been modified to include the generic and brand name in many instances.

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