Population Pharmacokinetics of Nifedipine in High-Altitude and Plain Patients with Hypertension

The pharmacokinetic characteristics of drugs are altered under high-altitude hypoxia. We aim to describe the population pharmacokinetics of nifedipine to investigate the effects of high-altitude hypoxia on the pharmacokinetics of nifedipine in hypertensive patients. A total of 206 plasma concentrations were collected from 50 patients with hypertension in plateau areas and 53 in plain areas. The PK of nifedipine in hypertensive patients in the plateau and plain area of China was described using nonlinear mixed-effects modeling. The patient's blood pressure was recorded to evaluate the antihypertensive effect of nifedipine. The pharmacokinetics of nifedipine were described by a one-compartment model with zero-order absorption and first-order elimination. The estimated apparent clearance was 18.74 L/h with 31.91% interindividual variability, and the apparent volume of distribution was 103.88 L with 22.44% interindividual variability. Plateau versus plains were identified as a significant covariate affecting nifedipine pharmacokinetics, particularly in inter-individual clearance rates. The interindividual variability of CL was reduced from 36.26% to 31.91%, and the CL of patients in the plateau area was about 1.35 times higher than that in the plain area. This study may contribute to the rational use of nifedipine in the plateau area.