Precision redosing of oritavancin: A population pharmacokinetic framework to optimize long-term therapy for complex...

We conducted a population pharmacokinetic (PK) analysis of patients receiving repeated oritavancin doses with therapeutic drug monitoring (TDM) to identify informative sampling times, and evaluate redosing strategies across extended intervals.

Plasma concentrations from adults treated with oritavancin at our centre were analysed using nonlinear mixed-effects modelling. Covariates were evaluated through forward-selection and backward-elimination. Model diagnostics and comparison to regulatory review were performed. Monte Carlo simulations (n = 1000 per regimen) were performed to evaluate accumulation, probability of target attainment (PTA) for AUC₇₂ ≥1498 mg·h/L, and trough maintenance ≥2.5 mg/L for weekly to every-four-week dosing.

Twenty-three patients contributed 249 samples; two-thirds of cases received multiple doses (less than 2 months), with the longest use lasting 14 months. A three-compartment model best described the data, with parameter estimates consistent with FDA review. Simulated regimens demonstrated meaningful accumulation, with median accumulation indices of 3.5, 2.9, 2.2 and 1.9 for weekly, biweekly, triweekly and every-four-week dosing, respectively. PTA for AUC₇₂ was 76% after the first dose and 100% at steady state for weekly and biweekly regimens. A single 24-h concentration strongly predicted AUC₇₂ (R² = 0.93). Day-7 concentrations (C₁₆₈) effectively distinguished patients likely to maintain trough targets on 1-, 2-, or 3-week intervals; <5% were predicted to meet targets with 4-week dosing.

Repeated-dose oritavancin exhibits predictable PK suitable for individualised redosing. Concentrations at 24 and 168 h provide guidance for selecting 1-, 2-, or 3-week intervals. In the absence of TDM, weekly dosing offers the highest probability of achieving PK/PD targets.