Population Pharmacokinetics of Atorvastatin in High-Altitude and Plain Patients with Hyperlipidemic

The pharmacokinetic (PK) characteristics of drugs were altered under high-altitude hypoxia. We aim to describe the population PK of atorvastatin (ATV) to identify patient characteristics that are predictive of variability in the PK parameters of the ATV and investigate the effects of high-altitude hypoxia on the blood concentration of ATV in patients with hyperlipidemia. A total of 160 plasma concentrations were collected from 40 patients with hyperlipidemia in plateau areas and 40 in plain areas. The population pharmacokinetic model of patients with hyperlipidemia in plateau and plain areas of China was established by a nonlinear mixed-effects model. The PK of ATV were described by a 1-compartment model with first-order elimination. The main PK parameters of ATV were the first-order absorption rate (0.76 hour^-1 fixed); clearance (174.22 L/h) and apparent volume of distribution (1119.62 L). The values of area and age were identified as significant covariates for the clearance, area, age, and urea for the volume of distribution. The steady-state peak concentration in the plateau area was higher than that in the plain area. This study may suggest dose reduction is necessary for patients with hyperlipidemia in high altitudes.