Amlodipine pharmacokinetics in healthy volunteers

In the present study we investigated the pharmacokinetics and comparative bioavailability of three oral doses of amlodipine in 12 healthy male volunteers. A randomized, open-label, three period crossover study design was employed. Each subject received, on three separate occasions a single oral dose of 2.5, 5 and 10 mg amlodipine. Standing diastolic blood pressure was reduced by 1.1, 4.8 and 8 mmHg six hours after 2.5, 5 and 10 mg amlodipine, respectively. There were no significant changes in pulse rate, nor on the EKG. The curves for the mean plasma concentrations versus time for the three doses showed parallel time-courses. Highly significant positive correlations were observed between dose and AUC (0-72 hrs) and between dose and Cmax. However, dose corrected AUC and Cmax were 10-20% lower with 2.5 mg, than with 5 and 10 mg. Peak levels were achieved 5.6 to 6.4 hours postdose. Half lives were 31.2, 33 and 36.8 hours for 2.5, 5 and 10 mg respectively. Headache was the most common side effect, and was more frequently observed with the highest dose. In summary, linear relationships were found between the dose and the plasma levels of amlodipine. Decreases in standing diastolic blood pressure were also dose related. Because of its long half-life and gradual absorption, amlodipine should be effective in lowering blood pressure given once daily and the incidence of side effects due to rapid absorption should be minimized.