Amlodipine--does the effect-time profile directly reflect the concentration-time profile throughout a 24-hour period?

Two studies were undertaken to investigate correlations between the time profile of plasma drug concentration and the time profile of hypotensive activity for the dihydropyridine calcium antagonist, amlodipine. The first study compared the concentration- and effect-time profiles for amlodipine and felodipine ER (extended release), and the second study characterized the concentration-effect relationship in hypertensive patients. The inter- and intra-subject variabilities in the disposition characteristics of amlodipine were less than for felodipine and there was correspondingly less variability in plasma drug concentrations; trough-to-peak ratios were calculated as 67 +/- 8% for amlodipine and 36 +/- 13% for felodipine ER. The characteristics of the plasma-concentration profiles appeared to be reflected in the profiles of hypotensive response such that, although the peak effect with felodipine ER was greater, there was less variability with amlodipine and the trough effect with amlodipine was consistently superior. Examination of the relationship between the plasma concentrations of amlodipine and the antihypertensive effect revealed that, although there was a temporal discrepancy between the two profiles, the two could be correlated using a linear-effect model. Results of this analysis indicated that the kinetic-dynamic model was most appropriately fitted simultaneously to the acute and steady-state data. Thus, the low inter- and intra-subject variabilities in the disposition characteristics of amlodipine are translated into a consistent and smoothly sustained 24-h antihypertensive response.