INTRAINDIVIDUAL VARIABILITY IN NIFEDIPINE PHARMACOKINETICS AND EFFECTS IN HEALTHY-SUBJECTS

The intraindividual variability in pharmacokinetics and effects of oral nifedipine (10 mg), administered with 1 week intervals, was investigated in twelve young healthy subjects. The population estimate of the coefficient of intraindividual variability (CVw) in AUC of nifedipine (13%) was much smaller than the pure between-subject variability (CV(b) 54%). The long-term (1 1/2 year) intraindividual variability was much larger than the short-term variability. Maximum changes from baseline-values of mean blood pressure (SBP - 5%, DBP - 4%) and mean heart rate (HR + 21%) were small. Individual maximum changes in systolic blood pressure, diastolic blood pressure, and heart rate (SBP, DBP, and HR) and areas under effect curves were highly variable (CV(w) 34-250%, CV(b) 8-88%). For most subjects a significant positive linear relation was observed between nifedipine plasma concentration and the change in HR (mean r = 0.63). The CV(w) in slope (106%) and intercept (685%) were even larger than the high CV(b) in these parameters (38%) and 252%). Changes in blood pressure were not significantly related to nifedipine plasma concentrations within these healthy subjects. The small intraindividual variability in nifedipine pharmacokinetics allows crossover studies to detect pharmacokinetic relationships between nifedipine and other dihydropyridine calcium entry blockers.