Population Pharmacokinetics of Linezolid in Healthy Chinese Adults: Absorption Characteristics and Exploratory ABCB1-Related Variability

Background/Objectives: Linezolid has almost complete oral bioavailability, yet systemic exposure varies substantially between individuals. Food delays absorption, and genetic variation in ABCB1 may also contribute. We developed a population pharmacokinetic model to characterize these sources of variability. Methods: Plasma concentration–time data were analyzed after a single 600 mg oral dose of the reference product ZYVOX® in 48 healthy Chinese adults from two independent fasting and fed cohorts (n = 24 each) of a randomized crossover bioequivalence study. Nonlinear mixed-effects modeling (Monolix 2024R1) was used to characterize linezolid absorption and disposition and to evaluate covariates, including food status, sex, and ABCB1 variants. Model adequacy was assessed using standard diagnostics, including prediction-corrected visual predictive checks. Results: A one-compartment model with linear elimination and sequential zero- to first-order absorption with a lag time best described the data. Food status was retained as a covariate on absorption lag time (Tlag; 0.075 h fasting vs. 0.25 h fed), whereas effects on the other absorption parameters were not retained. ABCB1 C1236T genotype was associated with apparent oral clearance (CL/F; 5.00 L/h in T/T, 5.77 L/h in C/T, and 7.36 L/h in C/C carriers). The reference estimates of CL/F and V/F were 5.00 L/h (RSE 3.78%) and 43.78 L (RSE 2.03%). Conclusions: The sequential absorption model identified a food-related difference in Tlag and an association between ABCB1 C1236T genotype and apparent oral clearance. These findings may help interpret food-related changes in bioequivalence data and provide a candidate model for future evaluation in patients.