title: Lack of pharmacokinetic drug interactions following concomitant administration of telavancin with aztreonam or piperacillin/tazobactam in healthy participants.
abstract: This randomized crossover study in healthy participants assessed pharmacokinetic interactions between telavancin, aztreonam, and piperacillin/tazobactam. Part 1: 11 participants received telavancin 10 mg/kg, aztreonam 2 g, or a combination of telavancin 10 mg/kg+aztreonam 2 g intravenously on 3 separate days. Part 2: 12 participants received telavancin 10 mg/kg, piperacillin/tazobactam 4.5 g, or a combination of telavancin 10 mg/kg+piperacillin/tazobactam 4.5 g intravenously on 3 separate days. Blood and urine drug concentrations were measured up to 48 hours posttreatment. Drug interactions were assessed by equivalence analysis of noncompartmental pharmacokinetic parameters, focusing on area under plasma concentration-time curves (AUC), log transformed; if the antilog of the 90% confidence intervals (CIs) for the mean log AUC difference was within equivalence bounds (0.70, 1.43), the effect of coadministration on the pharmacokinetics of the respective drug was deemed not clinically significant. Plasma concentration-time curves for all treatment pairs were nearly superimposable with comparable values for pharmacokinetic parameter estimates. In equivalence analyses, 90% CI for the mean difference in log AUC in each comparison fell within the predefined clinical equivalence limits and bioequivalence limits (0.80, 1.25). Administration of aztreonam or piperacillin/tazobactam with telavancin had no clinically significant effect on the pharmacokinetic disposition of any of these drugs.
authors.affiliation: Theravance, Inc, 901 Gateway Blvd, South San Francisco, CA 94080, USA.
authors.forename: Shekman L
authors.initials: SL
authors.lastname: Wong
authors.forename: Fritz
authors.initials: F
authors.lastname: Sörgel
authors.forename: Martina
authors.initials: M
authors.lastname: Kinzig
authors.forename: Michael R
authors.initials: MR
authors.lastname: Goldberg
authors.forename: Michael M
authors.initials: MM
authors.lastname: Kitt
authors.forename: Steven L
authors.initials: SL
authors.lastname: Barriere
mesh_terms: D000293:Adolescent; D000328:Adult; D000617:Aminoglycosides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D001398:Aztreonam / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004408:Dysgeusia / Q000139:chemically induced; D005260:Female; D006801:Humans; D000077427:Lipoglycopeptides; D008297:Male; D008875:Middle Aged; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D010878:Piperacillin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000077725:Piperacillin, Tazobactam Drug Combination
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077427:Lipoglycopeptides; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D001398:Aztreonam; D010878:Piperacillin; C487637:telavancin