Vasospastic Angina NORVASC has been demonstrated to block constriction and restore blood flow in coronary arteries and arterioles in response to calcium, potassium epinephrine, serotonin, and thromboxane A2 analog in experimental animal models and in human coronary vessels in vitro. This inhibition of coronary spasm is responsible for the effectiveness of NORVASC in vasospastic (Prinzmetal's or variant) angina. Pharmacokinetics and Metabolism After oral administration of therapeutic doses of NORVASC, absorption produces peak plasma concentrations between 6 and 12 hours. Absolute bioavailability has been estimated to be between 64 and 90%. The bioavailability of NORVASC is not altered by the presence of food. NORVASC is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine. Ex vivo studies have shown that approximately 93% of the circulating drug is bound to plasma proteins in hypertensive patients. Elimination from the plasma is biphasic with a terminal elimination half-life of about 30-50 hours. Steady-state plasma levels of NORVASC are reached after 7 to 8 days of consecutive daily dosing. The pharmacokinetics of NORVASC are not significantly influenced by renal impairment. Patients with renal failure may therefore receive the usual initial dose. Elderly patients and patients with hepatic insufficiency have decreased clearance of amlodipine with a resulting increase in AUC of approximately 40-60%, and a lower initial dose may be required. A similar increase in AUC was observed in patients with moderate to severe heart failure. Pediatric Patients Sixty-two hypertensive patients aged greater than 6 years received doses of NORVASC between 1.25 mg and 20 mg. Weight-adjusted clearance and volume of distribution were similar to values in adults. | ||||
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