The effects of genetic polymorphisms of ABCB1 C3435T, POR*28, CYP3A4*1G and CYP3A5*3 variants and gender relating to metabolism on the exposure and response of amlodipine in Chinese hypertensive patients were determined. Population pharmacokinetic analyses were performed on data which were collected prospectively from 60 Chinese patients with mild to moderate essential hypertension [age range 40-74 years, males (n = 31), females (n = 29)] receiving oral racemic amlodipine for 4 weeks. Blood pressure was evaluated at the end of weeks 0 and 4. Blood samples were collected in heparinized tubes at the following times: 0, 2, 6, and 24 h on about day 28 after administration of amlodipine. A one-compartment model with first-order elimination and absorption best described the amlodipine pharmacokinetic data. ABCB1 3435 genetic polymorphism and gender affect the amlodipine oral clearance (CL/F). CL/F (L/h) = 28.8 × (1 + GNDR)(-0.531) × (ABCB1 C3435T) where GNDR = 0 and 1 are for male and female, respectively. The CL/F value in a male patient with the ABCB1 3435CC or CT genotype is 28.8 L/h. Lower CL/F and higher exposure occurs in female subjects with the ABCB1 3435CC or CT genotype who have greater decreases in blood pressure after treatment with amlodipine. The results may help to improve the efficacy and tolerability of amlodipine in essential hypertensive patients.