Race and sex influence clearance of nifedipine: Results of a population study

Objective: To estimate oral clearance of nifedipine and to determine demogr aphic and clinical covariates that affect nifedipine clearance in a clinica l population. Methods: Apparent oral clearance of nifedipine and protein binding were mea sured in 226 patients receiving sustained-release nifedipine formulations f or hypertension and corollary artery disease (black men, n = 111; black wom en, n = 27; white men, n = 64; white women, n = 24), Mean age +/- SD was 71 +/- 11 pears, and mean weight was 86 +/- 17 kg. Nifedipine concentrations were analyzed by HPLC, protein binding was measured by equilibrium dialysis , clearance and covariate effects were estimated by a nonlinear mixed effec ts population model, and statistical analyses were performed by a nonlinear mix-ed-effects model (clearance) and ANOVA (protein binding). Results:Clearance was significantly slower in black subjects (8.9 +/- 0.7 m L/min/kg; mean +/- SE) compared with white subjects (11.6 +/- 0.8 ml/min/kg ; P=.00004) and in men compared with women (9.3 +/- 0.6 versus 12.1 +/- 1.5 mL/min/kg; P=.0021). Reported alcohol use (alcohol, 8.6 +/- 1.1 versus no alcohol, 10.8 +/- 0.6 mL/min/kg; P =.0002) and smoking status (smoker, 8.8 +/- 2.0 versus nonsmoker, 10.2 +/- 0.6 mL/min/kg; P =.0362) also affected n ifedipine clearance. Race and sex had no effect on protein binding of nifed ipine (P =.29 and P =.44, respectively). No effects of age, stable coronary artery disease, or reported intake of beta-blockers on nifedipine clearanc e were detected in this primarily elderly population with hypertension. Conclusions: The data suggest that race, sex, and environmental factors are identifiable sources of interindividual variation in the oral clearance of nifedipine, a CYP3A substrate. Our experience also suggests that data from clinical populations may be biased with regard to age, sex, and formulatio n selection, and covariates may not be independently distributed, which can limit analyses.