PHARMACOKINETICS AND PHARMACODYNAMICS OF AMLODIPINE IN COMPARISON WITH NIFEDIPINE AR IN PATIENTS WITH MILD TO MODERATE HYPERTENSION

The pharmacokinetic and pharmacodynamic properties of single and multiple oral doses of 10 mg of amlodipine once daily, a new calcium antagonist, in comparison with 20 mg of nifedipine AR BID, were investigated in eight patients with mild to moderate hypertension. The two drugs did not change heart rate either after the first or steady-state administrations. Nifedipine showed a marked and rapid reduction in blood pressure followed by a slow decrease of the effect, which was practically absent eight to 12 hours after administration. After amlodipine administration, reduction in blood pressure was smoother and reached its maximum after six hours and, when the drug reached the steady state, an adequate control of blood pressure was obtained 24 hours after administration. A one-compartment model was developed from multiexponential fitting of plasma concentrations of amlodipine and nifedipine AR for the pharmacokinetic study. Amlodipine has a half-life (t1/2) of 36.65 +/- 4.27 hours, which is about four times the nifedipine AR half-life (t1/2 = 8.58 +/- 0.88 hours). The apparent distribution volume of amlodipine (V = 263.52 +/- 54.67 L) is three or four times larger than that of nifedipine AR. The estimates of the pharmacokinetic and pharmacodynamic properties of amlodipine indicate that it is potentially convenient for once-daily administration.