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Clinical Pharmacokinetics and Pharmacodynamics of Dalbavancin

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Abstract

Dalbavancin is a synthetic lipoglycopeptide that exerts its antimicrobial activity through two distinct modes of action, inhibition of cell wall synthesis and an anchoring mechanism. Compared with previous glycopeptide antibiotics, dalbavancin demonstrates improved antibacterial potency against Gram-positive organisms and a long half-life of approximately 1 week, which is longer in tissues (e.g., skin, bone) than plasma. These factors facilitated the development of single-dose or once-weekly dosing regimens to treat acute bacterial skin and skin structure infections (ABSSSI). Dalbavancin exhibits dose-proportional pharmacokinetics and is highly protein bound (93%). Despite being highly protein bound, it has a steady-state volume of distribution >10 L and distributes widely into the skin, bone, peritoneal space, and epithelial lining fluid, but not cerebrospinal fluid. Dalbavancin elimination occurs via a combination of renal (approximately 45%) and non-renal clearance, with dose adjustments recommended only in patients with a creatinine clearance <30 mL/min not receiving any form of dialysis. The established pharmacokinetic/pharmacodynamic index associated with bacterial kill is free area under the concentration-time curve over the minimum inhibitory concentration (fAUC/MIC), with a goal 24-h fAUC/MIC of at least 27.1 for Staphylococcus aureus infections. Recent data suggest usefulness in the treatment of infections beyond ABSSSI, with convenient dosing and redosing strategies for complicated infections requiring extended treatment durations. Additional studies are needed to confirm these preliminary findings.

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Fig. 1

Adapted from the dalbavancin European Medicines Agency package insert (https://www.medicines.org.uk/emc/product/2270/smpc#gref) and Carrothers et al. [25]. Population pharmacokinetic data are from the DUR001-303 phase IIIb study [3]

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Authors and Affiliations

  1. Department of Pharmacy Services, University of Colorado Hospital, Aurora, CO, USA

    Kyle C. Molina, Matthew A. Miller, Scott W. Mueller & Tyree H. Kiser

  2. Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, 12850 E. Montview Blvd Mail Stop C238, Aurora, CO, 80045, USA

    Kyle C. Molina, Matthew A. Miller, Scott W. Mueller & Tyree H. Kiser

  3. Clinical Pharmacy and Translational Science, University of Tennessee Health Sciences Center College of Pharmacy, Memphis, TN, USA

    Edward T. Van Matre

  4. Department of Medicine, Division of Infectious Diseases, University of Colorado School of Medicine, Aurora, CO, USA

    Kyle C. Molina, Matthew A. Miller & Martin Krsak

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Correspondence to Tyree H. Kiser.

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Tyree H. Kiser reports previous investigator-initiated dalbavancin research funding paid to his institution from Allergan Pharmaceuticals. Matthew A. Miller reports participation in the speaker’s bureau for Allergan Pharmaceuticals. Kyle C. Molina, Scott W. Mueller, Edward Van Matre, and Martin Krsak have no disclosures to declare.

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Molina, K.C., Miller, M.A., Mueller, S.W. et al. Clinical Pharmacokinetics and Pharmacodynamics of Dalbavancin. Clin Pharmacokinet 61, 363–374 (2022). https://doi.org/10.1007/s40262-021-01088-w

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