Pharmacokinetics and excretion of dalbavancin in the rat.
OBJECTIVE
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 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 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.
Cavaleri
Marco
M
Vicuron Pharmaceuticals Italy, Via R. Lepetit 34-21040, Gerenzano, Varese, Italy. mcavaleri@vicuron.it
Riva
Simona
S
Valagussa
Anna
A
Guanci
Marco
M
Colombo
Luigi
L
Dowell
James
J
Stogniew
Martin
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D006020:Glycopeptides / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017334:Teicoplanin / Q000031:analogs & derivatives; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D017334:Teicoplanin; C469289:dalbavancin