Plasma concentration-response relationships for some cardiovascular effects of dihydropyridines in healthy subjects

The pharmacokinetics and some hemodynamic effects of three dihydropyridine (DHP) calcium channel blockers were studied in healthy subjects. In a randomized order, each subject was given 24 micrograms/kg nifedipine, 40 micrograms/kg nitrendipine, or 10 micrograms/kg nisoldipine intravenously. The three DHPs differed as to their total clearance and volume of distribution (nifedipine less than nisoldipine less than nitrendipine) but showed similar values for elimination half-lives. All three drugs evoked increases in heart rate and forearm blood flow (FBF) and small decreases in blood pressure. Whereas the observed peak changes in heart rate were virtually identical for the three drugs (about 45% above baseline), the peak changes in FBF were more pronounced in response to nitrendipine and nisoldipine (greater than 200% above baseline) than in response to nifedipine (79% above baseline). The heart rate and FBF responses to the DHPs were related directly to the drug concentrations in plasma. The plasma level-response curves obeyed Hill's equation. They showed that the DHPs differ mainly in their potencies at dilating the forearm resistance vessels (nifedipine less than nitrendipine less than nisoldipine).