{Reference Type}: Clinical Trial, Phase II
{Title}: Dalbavancin Population Pharmacokinetic Modeling and Target Attainment Analysis.
{Author}: Carrothers TJ;Chittenden JT;Critchley I;
{Journal}: Clin Pharmacol Drug Dev
{Volume}: 9
{Issue}: 1
{Year}: 01 2020
暂无{DOI}: 10.1002/cpdd.695
{Abstract}: 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.