Differences in nifedipine concentration-effect relationship between capsule and slow release tablet administration.
The relationships between nifedipine plasma concentrations and its hypotensive and positive chronotropic effects were studied in healthy volunteers who received either a 10 mg capsule (CAP) or a 20 mg slow release tablet (SRT). Plasma concentrations rose more rapidly after CAP than after SRT, Cmax being 131 +/- 39 and 40 +/- 7 ng/ml and tmax being 0.5 +/- 0.07 and 1.8 +/- 0.4 h, respectively. Both formulations produced a reduction in diastolic blood pressure which exhibited a significant linear correlation (p < 0.01) with nifedipine plasma concentration. However, the slope obtained with SRT was significantly higher than that of CAP (0.24 +/- 0.05 vs 0.07 +/- 0.01, p < 0.01). That is, a similar hypotensive effect was produced at a lower concentration with SRT than with CAP. A positive chronotropic effect which exhibited a highly significant correlation with nifedipine plasma concentration (p < 0.0001) was observed with CAP. Conversely, with SRT heart rate increase was smaller and there was no significant correlation with nifedipine plasma concentration (p > 0.45). Since the measured decrease in blood pressure is the outcome of nifedipine-induced vasodilation and of homeostatic responses, results are interpreted as follows. Fast nifedipine input after CAP induced a brisk change in physiological conditions and hence triggered an important homeostatic response, visualized as heart rate increase, which partially offset the hypotensive effect. With SRT, there was a gradual change in blood pressure producing lesser activation of compensatory mechanisms and therefore the hypotensive effect of nifedipine was less antagonized than with CAP. Nifedipine SRT does not only exhibit pharmacokinetic advantages, but also a more favorable pharmacodynamic profile than CAP.
Castañeda-Hernández
G
G
Departamento de Farmacología y Toxicología, Instituto Politécnico Nacional, Mexico City, Mexico.
Hoyo-Vadillo
C
C
Herrera
J E
JE
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002214:Capsules; D003692:Delayed-Action Preparations; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D013607:Tablets; D013997:Time Factors
D002214:Capsules; D003692:Delayed-Action Preparations; D013607:Tablets; D009543:Nifedipine