Dalbavancin Population Pharmacokinetic Modeling and Target Attainment Analysis.

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.

• Authors: Timothy J Carrothers, Jason T Chittenden, Ian Critchley
• Journal: Clinical pharmacology in drug development (Clin Pharmacol Drug Dev) Vol. 9 Issue 1 Pg. 21-31 (01 2020) ISSN: 2160-7648 [Electronic] United States
• PMID: 31087630 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Chemical References

• Anti-Bacterial Agents
• Teicoplanin
• dalbavancin

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (pharmacokinetics, pharmacology)
• Area Under Curve
• Bacteria (drug effects, growth & development)
• Female
• Humans
• Male
• Microbial Sensitivity Tests
• Middle Aged
• Models, Biological
• Teicoplanin (analogs & derivatives, pharmacokinetics, pharmacology)
• Young Adult