Dalbavancin Population Pharmacokinetic Modeling and Target Attainment Analysis

Dalbavancin is indicated for the treatment of acute bacterial skin and skin structure infections caused by susceptible gram‐positive microorganisms. This analysis represents the update of the population pharmacokinetics (popPK) modeling and target attainment simulations performed with data from the single‐dose safety and efficacy study and an unrelated but substantial revision of the preclinical pharmacokinetic/pharmacodynamic target (fAUC/MIC, free area under concentration‐time curve/minimum inhibitory concentration ratio). A 3‐compartment distribution model with first‐order elimination provided an appropriate fit, with typical dalbavancin clearance of 0.05 L/h and total volume of distribution of ∼15 L. Impact of intrinsic factors was modest, although statistically significant (P < .05) relationships with total clearance were found for the following covariates: creatinine clearance, weight, and albumin — dose adjustment was only indicated for severe renal impairment. Under the new nonclinical target, simulations of the popPK model projected that >99% of subjects would achieve the nonclinical target at MIC values up to and including 2 mg/L.