Pharmacokinetics and excretion of dalbavancin in the rat

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 [ 3 H]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 t 1/2 of 187h (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 t 1/2 (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.