Model-informed precision dosing of quetiapine in bipolar affective disorder patients: initial dose recommendation

Abstract

Objective: Bipolar affective disorder (BAD) is a mood disorder with high morbidity and mortality. Quetiapine can be used in the treatment of patients with BAD; however, the precise administration regimen of quetiapine in these patients is still unknown. In this study, a population pharmacokinetic (PPK) model of quetiapine in patients with BAD was constructed based on model-informed precision dosing (MIPD) and real-world clinical data and an optimal initial dose of quetiapine in these patients was recommended. Methods: A total of 99 patients with BAD treated with quetiapine were included. At the same time, the quetiapine concentrations, the physical and chemical indices of the patients, and the drug combination information were collected. A quetiapine PPK model for patients with BAD was then constructed and an initial dose based on Monte Carlo simulation was recommended. Results: In the final model of quetiapine for patients with BAD, the apparent oral clearance (CL/F) and the apparent volume of distribution (V/F) were 76.1 L/h and 530 L, respectively. For patients with BAD weighing 40–66 kg, the initial dose recommendation was 16 mg kg−1 day−1, the probability of reaching the therapeutic window was 78.8%–82.2%, and the probability of exceeding the upper limit of the therapeutic window was 5.2%–10.3%. For patients with BAD weighing 66–120 kg, the initial dose recommendation was 12 mg kg−1 day−1, the probability of reaching the therapeutic window was 81.5%–85.5%, and the probability of exceeding the upper limit of the therapeutic window was 3.6%–8.1%. Conclusion: The present study, for the first time, recommended an initial dose of quetiapine in patients with BAD based on MIPD and real-world data, providing an individualized reference for the administration of quetiapine in these patients.