Publication: CPT: Pharmacometrics & Systems Pharmacology (PSP)
Abstract
This publication describes a population pharmacokinetic (PopPK) analysis of dolutegravir in plasma and cerebrospinal fluid (CSF) in adults living with HIV. Using data from 121 treatment-experienced adults receiving dolutegravir-based antiretroviral therapy, researchers developed a model to characterize systemic drug exposure and the rate and extent of penetration into the central nervous system. The analysis demonstrated rapid plasma-to-CSF equilibration but relatively low steady-state CSF penetration and identified an inverse relationship between body mass index and dolutegravir exposure. The findings demonstrate how population PK modeling can provide a more complete understanding of drug distribution into difficult-to-measure compartments and help inform clinical development, trial design, and population-specific dosing considerations.
Authors: Ahmed A. Abulfathi (Certara), Mohammed W. Ali, Sam Nightingale, Tracy Kellermann, John Joska, Alan Winston, Saye Khoo, Joseph F. Standing, Eric H. Decloedt
Published: 2026 年 9 月 29 日
Understand drug exposure beyond plasma
Characterizing drug exposure in difficult-to-measure compartments such as cerebrospinal fluid can be critical to understanding whether therapies reach their intended site of action. Certara’s pharmacometrics experts use population PK modeling and simulation to quantify drug disposition, identify sources of variability, and translate complex clinical data into evidence that can inform dosing and development decisions.
