Race and sex influence clearance of nifedipine: Results of a population study
Race and sex influence clearance of nifedipine: Results of a population study
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DOI：
10.1067/mcp.2000.108678
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发表时间：
2000-08-01
影响因子：
6.7
通讯作者：
Schwartz, JB
中科院分区：
文献类型：
--
作者：
Krecic-Shepard, ME;Park, K;Schwartz, JB
目的：方法：对226例接受硝苯地平缓释制剂治疗高血压和冠状动脉疾病的患者进行硝苯地平表观口服清除率和蛋白结合率测定（黑人男性，n = 111;黑人女性，n = 27;白色男性，n = 64;白色女性，n = 24），平均年龄+/- SD为71 +/-11梨，平均体重为86 +/-17 kg。硝苯地平浓度采用HPLC分析，蛋白结合采用平衡透析法测定，清除率和协变量效应采用非线性混合效应群体模型估计，统计学分析采用非线性混合效应模型（清除率）和ANOVA结果：在黑人受试者中，（8.9 +/- 0.7 mL/min/kg;平均值+/- SE）与白色受试者（11.6 +/- 0.8 mL/min/kg; P=.00004）相比，男性与女性相比（9.3 +/- 0.6 vs 12.1 +/- 1.5 mL/min/kg; P=.0021）。报告的饮酒（饮酒，8.6 +/- 1.1 vs无饮酒，10.8 +/- 0.6 mL/min/kg; P =.0002）和吸烟状态（吸烟者，8.8 +/- 2.0 vs非吸烟者，10.2 +/- 0.6 mL/min/kg; P =.0362）也影响硝苯地平清除率。种族和性别对硝苯地平的蛋白结合没有影响（分别为P = 0.29和P = 0.44）。年龄，稳定的冠状动脉疾病，或报告的β-受体阻滞剂的摄入量对硝苯地平清除率没有影响，在这主要是老年人人口高血压。结论：数据表明，种族，性别和环境因素是可识别的个体间变异的硝苯地平，CYP 3A底物的口服清除率的来源。我们的经验还表明，临床人群的数据可能在年龄、性别和制剂选择方面存在偏倚，协变量可能不是独立分布的，这可能会限制分析。
Objective: To estimate oral clearance of nifedipine and to determine demographic and clinical covariates that affect nifedipine clearance in a clinical population.Methods: Apparent oral clearance of nifedipine and protein binding were measured in 226 patients receiving sustained-release nifedipine formulations for hypertension and corollary artery disease (black men, n = 111; black women, 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 effects 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 mL/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 nifedipine clearance. Race and sex had no effect on protein binding of nifedipine (P =.29 and P =.44, respectively). No effects of age, stable coronary artery disease, or reported intake of beta-blockers on nifedipine clearance 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 formulation selection, and covariates may not be independently distributed, which can limit analyses.