Nicardipine HCl plasma levels were higher in patients with mild renal impairment (baseline serum creatinine concentration ranged from 1.2 to 5.5 mg/dl) than in normal subjects. After 30 mg nicardipine HCl TID at steady state, Cmax and AUC were approximately 2-fold higher in these patients.

Because nicardipine HCl is extensively metabolized by the liver, the plasma levels of the drug are influenced by changes in hepatic function. Nicardipine HCl plasma levels were higher in patients with severe liver disease (hepatic cirrhosis confirmed by liver biopsy or presence of endoscopically confirmed esophageal varices) than in normal subjects. After 20 mg nicardipine HCl BID at steady state, Cmax and AUC were 1.8 and 4-fold higher, and the terminal half-life was prolonged to 19 hours in these patients.

Hemodynamics

In man, nicardipine HCl produces a significant decrease in systemic vascular resistance. The degree of vasodilation and the resultant hypotensive effects are more prominent in hypertensive patients. In hypertensive patients, nicardipine reduces the blood pressure at rest and during isometric and dynamic exercise. In normotensive patients, a small decrease of about 9 mmHg in systolic and 7 mmHg in diastolic blood pressure may accompany this fall in peripheral resistance. An increase in heart rate may occur in response to the vasodilation and decrease in blood pressure, and in a few patients this heart rate may be pronounced. In clinical studies mean heart rate at time of peak plasma levels was usually increased by 5-10 beats per minute compared to placebo, with the greater increases at higher doses, while there was no difference from placebo at the end of the dosing interval. Hemodynamic studies following intravenous dosing in patients with coronary artery disease and normal or moderately abnormal left ventricular function have shown significant increases in ejection fraction and cardiac output with no significant change, or a small decrease, in left ventricular end-diastolic pressure (LVEDP). Although there is evidence that nicardipine HCl increases coronary blood flow, there is no evidence that this property plays any role in its effectiveness in stable angina. In patients with coronary artery disease, intracoronary administration of nicardipine caused no direct myocardial depression. Nicardipine HCl does, however, have a negative inotropic effect in some patients with severe left ventricular dysfunction and could, in patients with very impaired function, lead to worsened failure.

"Coronary Steal", the detrimental redistribution of coronary blood flow in patients with coronary artery disease (diversion of blood from underperfused areas toward better perfused areas), has not been observed during nicardipine treatment. On the contrary, nicardipine has been shown to improve systolic shortening in normal and hypokinetic segments of myocardial muscle, and radio-nuclide angiography has confirmed that wall motion remained improved during an increase in oxygen demand. Nonetheless, occasional patients have developed increased angina upon receiving nicardipine. Whether this represents steal in those patients, or is the result of increased heart rate and decreased diastolic pressure, is not clear.

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