Journal Article

Pharmacokinetics and excretion of dalbavancin in the rat

Marco Cavaleri, Simona Riva, Anna Valagussa, Marco Guanci, Luigi Colombo, James Dowell and Martin Stogniew

in Journal of Antimicrobial Chemotherapy

Volume 55, issue suppl_2, pages ii31-ii35
Published in print March 2005 | ISSN: 0305-7453
Published online March 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki006
Pharmacokinetics and excretion of dalbavancin in the rat

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Objectives: The pharmacokinetics, tissue distribution and excretion routes of dalbavancin, a semi-synthetic glycopeptide, were investigated in rats.

Methods: A 20 mg/kg intravenous dose of dalbavancin or [3H]dalbavancin was administered to rats in three studies. Concentrations of dalbavancin or drug-derived radioactivity were assessed in blood, plasma, tissues, bile, urine and faeces by HPLC-MS/MS, scintillation counting or microbiological methods.

Results: Dalbavancin decayed tri-exponentially in plasma with an apparent terminal t1/2 of 187 h (approximately 8 days). Dalbavancin has dual routes of elimination, with around two-thirds of the excreted drug-derived radioactivity being found in the urine and around one-third in the faeces. After 70 days, 44.2% and 22.3% of the drug-derived radioactivity had been recovered in the urine and faeces, respectively. Biliary excretion of drug-derived radioactivity accounted for over half of the radioactivity excreted faecally. At 70 days post-dose, <5% of the dose remained in the carcass, showing that drug elimination was complete.

Conclusions: Dalbavancin has a long t1/2 (approximately 8 days) in the rat and distributes widely throughout the body. It is not selectively retained in any single organ, tissue or blood component and is completely eliminated by both renal and non-renal routes in rats. These data were useful in designing and interpreting animal infection model studies used to select the dose for human studies.

Keywords: glycopeptides; tissue distribution; mass balance

Journal Article.  0 words. 

Subjects: Medical Oncology ; Critical Care

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