Factors Influencing Quetiapine Pharmacokinetic Variability: a Review of Population Pharmacokinetics

Abstract

Atypical antipsychotic quetiapine (QTP) exhibits high pharmacokinetic variability and population pharmacokinetic (PopPK) analysis is one of the approaches used to characterize factors influencing QTP pharmacokinetic variability. Though QTP is not regarded as a narrow therapeutic index drug, knowledge of this area is of importance. Thus, this review was conducted to summarize significant predictors for QTP pharmacokinetic variability identified using a PopPK analysis and to explore any knowledge gaps to be investigated. PubMed, Scopus, and CINAHL Complete databases were searched for eligible studies, and 75 articles were identified. Of these, only five studies were included as they were conducted using a nonlinear mixed-effects approach. This review found that only limited predictors for QTP pharmacokinetics were identified, with body weight being a predictor for the volume of distribution and age and γ-glutamyl transpeptidase being predictors for QTP clearance. None of the studies included elderly patients aged >65 years, and thus factors associated with aging were not investigated. Also, most of the participants in the PopPK analyses were from clinical trials which might not reflect real-world patients e.g., the impacts of polypharmacy may not be available. Moreover, while a population pharmacokinetic-pharmacodynamic model explaining QTP exposure and clinical response using the scores of the Brief Psychiatric Rating Scale is available, knowledge relevant to the relationship between exposure and QTP side effects has not been explored. Based on this limited information, future PopPK research encompassing a wide range of patient characteristics is required.