Plasma concentration-effect relationship of felodipine intravenously in patients with congestive heart failure.
The pharmacodynamics of felodipine were analyzed in patients with congestive heart failure in a randomized, double-blind, placebo-controlled study. Felodipine at a dose of 1 mg (n = 11) or placebo (n = 12) was given intravenously during a 60-min period. Hemodynamic measurements and plasma samples were obtained every 15 min during a 2-hour period. An increase in heart rate (HR, +8%, p less than 0.01) and cardiac output (CO, +36%, p less than 0.001), and a decrease in mean arterial pressure (MAP, -24%, p less than 0.001) and systemic vascular resistance (SVR, -46%, p less than 0.001), were found. Pulmonary artery, right atrial, wedge pressure, and stroke-work index did not change. Linear regression analysis showed a significant correlation between felodipine plasma levels and changes in HR (r = 0.71, p less than 0.05), MAP (r = 0.94, p less than 0.01), CO (r = 0.73, p less than 0.05), and SVR (r = 0.88, p less than 0.01). A strong hyperbolic correlation was demonstrated between individual plasma levels and changes in MAP (r = 0.97, p less than 0.001). Hysteresis analysis showed that plasma levels are directly related to the concentration at the receptor site. A clockwise hysteresis was found in HR, CO, and SVR, but not in MAP. It is concluded that changes in flow and resistance are based on a physiological adjustment, a baroreflex-mediated response to vasodilation induced by felodipine, resulting in MAPs that remain closely related to felodipine plasma levels over a wide range.
Dunselman
P H
PH
Department of Cardiology, Groningen University, The Netherlands.
Edgar
B
B
Scaf
A H
AH
Kuntze
C E
CE
van Bruggen
A
A
Lie
K I
KI
Wesseling
H
H
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D015736:Felodipine; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009568:Nitrendipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D011897:Random Allocation; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D009568:Nitrendipine; D015736:Felodipine