Population Pharmacokinetics of Butylphthalide Injection in Elderly Chinese Patients With Ischemic Stroke

Abstract

Butylphthalide is widely used to treat acute ischemic stroke in China, and the main adverse effect is the increase in transaminase levels. We aimed to establish a population pharmacokinetic model of butylphthalide in elderly patients with ischemic stroke and identified covariates influencing butylphthalide pharmacokinetics. We collected butylphthalide blood samples via opportunistic sampling. We chose the base model, compared 1-, 2-, and 3-compartment models, and used basic patient information, laboratory test results, concomitant drugs, and comorbidities as covariates to examine our study. Our study included 50 patients (n = 106 blood samples), and a 2-compartment model with first-order elimination matched the experimental data well. Body weight and comorbid diabetes significantly affect the clearance of butylphthalide. On the basis of the final PPK model, the Monte Carlo method was used to compare the effects of different body weights and the state of diabetes on the steady-state area under the concentration–time curve at 0-24 hours. The results revealed that the steady-state area under the concentration–time curve at 0-24 hours was lower in patients with diabetes than in patients without diabetes, and both values decreased with weight gain. Our findings provide information for personalized treatment plans for patients with ischemic stroke (aged 65 years or older) receiving butylphthalide injection.