Vancomycin Population Pharmacokinetics and Exposure Variability in Children with Multiple Organ Dysfunction Syndrome

In children with multiple organ dysfunction syndrome (MODS), vancomycin dosing is frequently guided by population-based approaches followed by therapeutic drug monitoring that requires considerable blood volumes. We sought to develop a population pharmacokinetic (PK) model and describe vancomycin exposures using blood-sparing, whole-blood volumetric absorptive microsampling (VAMS). In this multicentre prospective observational study, up to 15 PK samples were collected per subject over 3 days. Individual whole-blood areas under the concentration-time curve during 0-24 hours (AUC_0-24h) and 24-48 hours (AUC_24-48h) after treatment initiation were estimated. Simulations explored exposures across weight and renal function strata. Sixty-five subjects were included in the final model cohort (median age, 10 years [range, 1 month-17 years]; median weight, 30 kg [3-214 kg]). A two-compartment, allometrically scaled model incorporating renal function best described vancomycin PK. The median dose preceding the first PK sample was 380 mg (15 mg/kg), with most subjects receiving vancomycin every 6 hours. In the fully paired analysis set (n=46), median whole-blood AUC_0-24h and AUC_24-48h were 475 mg·h/L (range, 232-1,749) and 594 mg·h/L (range, 188-2,157), respectively. Simulations demonstrated substantial exposure variability across weight and renal function strata. These findings demonstrate substantial interindividual exposure variability despite population-based dosing. The model provides a foundation for prospective evaluation of individualized exposure estimation using sparse VAMS sampling. Whole-blood VAMS AUC therapeutic targets remain unvalidated, and direct interpretation against established plasma-based targets is an important future effort.