Population pharmacokinetic analysis of dalbavancin, a novel lipoglycopeptide.
Dalbavancin is a lipoglycopeptide antibiotic in clinical development as a once-weekly treatment for serious infections. A total of 532 patients, consisting of 502 patients with skin and soft tissue infections requiring parenteral therapy and 30 patients with catheter-related bloodstream infections, was available for population pharmacokinetic analysis. The majority of patients (78.4%) received dalbavancin intravenously as a 1000-mg dose on day 1 and a single 500-mg dose on day 8. A 2-compartment model with first-order elimination provided the best fit to the data. The clearance of dalbavancin was influenced by body surface area and creatinine clearance, but together they described less than 25% of the interpatient variability. Body surface area was determined to be a predictor of the central volume of distribution. There was no evidence that the presence of metabolic substrates, inhibitors, or inducers of cytochrome P450 or selected concomitant medications influenced the clearance of dalbavancin.
Buckwalter
Mary
M
Vicuron Pharmaceuticals, King of Prussia, PA 19406, USA. mbuckwalter@vicuron.com
Dowell
James A
JA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001830:Body Surface Area; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006017:Glycolipids / Q000493:pharmacokinetics; D006020:Glycopeptides / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D017192:Skin Diseases, Bacterial / Q000188:drug therapy / Q000378:metabolism; D018461:Soft Tissue Infections / Q000188:drug therapy / Q000378:metabolism; D017334:Teicoplanin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D000900:Anti-Bacterial Agents; D006017:Glycolipids; D006020:Glycopeptides; C010762:peptidoglycolipids; D017334:Teicoplanin; C469289:dalbavancin; D003404:Creatinine