Do P-glycoprotein-mediated drug-drug interactions at the blood-brain barrier impact morphine brain distribution?

• Tác giả: Elizabeth Cm de Lange, Berfin Gülave, Ariel Lesmana, J G Coen van Hasselt
• Ngôn ngữ: eng
• Thông tin xuất bản: United States : Journal of pharmacokinetics and pharmacodynamics , 2025
• Bộ sưu tập: NCBI
• ID: 90129

Tóm tắt

P-glycoprotein (P-gp) is a key efflux transporter and may be involved in drug-drug interactions (DDIs) at the blood-brain barrier (BBB), which could lead to changes in central nervous system (CNS) drug exposure. Morphine is a P-gp substrate and therefore a potential victim drug for P-gp mediated DDIs. It is however unclear if P-gp inhibitors can induce clinically relevant changes in morphine CNS exposure. Here, we used a physiologically-based pharmacokinetic (PBPK) model-based approach to evaluate the potential impact of DDIs on BBB transport of morphine by clinically relevant P-gp inhibitor drugs.The LeiCNS-PK3.0 PBPK model was used to simulate morphine distribution at the brain extracellular fluid (brain