In this section
@article{Ali:2026:10.1002/psp4.70345,
author = {Ali, MW and Nightingale, S and Kellermann, T and Joska, J and Winston, A and Khoo, S and Standing, JF and Decloedt, EH and Abulfathi, AA},
doi = {10.1002/psp4.70345},
journal = {CPT Pharmacometrics Syst Pharmacol},
title = {Population Pharmacokinetics of Dolutegravir in Plasma and Cerebrospinal Fluid in Adults Living With HIV.},
url = {http://dx.doi.org/10.1002/psp4.70345},
volume = {15},
year = {2026}
}
TY - JOUR
AB - Characterizing dolutegravir penetration into the central nervous system is important for optimizing human immunodeficiency virus treatment outcomes, yet population-specific pharmacokinetic data describing cerebrospinal fluid disposition and equilibration kinetics remain lacking. This study characterizes dolutegravir pharmacokinetics in plasma and cerebrospinal fluid to describe the plasma-to-cerebrospinal fluid equilibration rate constant and cerebrospinal fluid-to-plasma pseudo-partition coefficient. Sparse pharmacokinetics samples were collected from 121 antiretroviral therapy-experienced adults who are predominantly overweight or obese (body mass index: 32.2 ± 8.7 kg/m2) receiving daily dolutegravir (50 mg)-based therapy. The model was developed using nonlinear mixed-effects modeling in NONMEM. Plasma dolutegravir pharmacokinetics were best described by a one-compartment model with first-order absorption and elimination. The population estimate for apparent oral clearance was 1.38 L/h/70 kg. Cerebrospinal fluid data were modeled using a sequential approach with a hypothetical effect compartment linked to plasma to estimate equilibration kinetics and relative cerebrospinal fluid exposure at steady-state. Key cerebrospinal fluid penetration parameters included a plasma-to-cerebrospinal fluid equilibration rate constant of 0.38 h-1, corresponding to an equilibration half-life of 1.82 h, and a cerebrospinal fluid-to-plasma pseudo-partition coefficient of 0.0015, indicating 0.15% cerebrospinal fluid penetration relative to plasma. Post hoc estimated area under the concentration-time curve (0-24) demonstrated a moderate inverse correlation with body mass index (r = -0.34), indicating that dolutegravir exposure decreases with increasing body mass index. The model revealed rapid plasma-to-cerebrospinal fluid equilibration kinetics with low steady-state cerebrospinal fluid penetration in this pre
AU - Ali,MW
AU - Nightingale,S
AU - Kellermann,T
AU - Joska,J
AU - Winston,A
AU - Khoo,S
AU - Standing,JF
AU - Decloedt,EH
AU - Abulfathi,AA
DO - 10.1002/psp4.70345
PY - 2026///
TI - Population Pharmacokinetics of Dolutegravir in Plasma and Cerebrospinal Fluid in Adults Living With HIV.
T2 - CPT Pharmacometrics Syst Pharmacol
UR - http://dx.doi.org/10.1002/psp4.70345
UR - https://www.ncbi.nlm.nih.gov/pubmed/42811541
VL - 15
ER -