Pharmacokinetics, Safety and Tolerability of Single Dose Dalbavancin in Children 12-17 Years of Age.

Background: Dalbavancin is a lipoglycopeptide antibiotic with Gram-positive activity and novel pharmacokinetic (PK) properties that result in a prolonged terminal half-life of 15.5 days in adults. Once weekly dosing in adults in phase 3 studies of complicated skin and skin structure infections documented dalbavancin exposures associated with clinical and microbiologic efficacy. PK properties have not been examined in children. The primary objective of this open-label, multicenter single-dose phase 1 study was to characterize the PK of dalbavancin in hospitalized pediatric subjects 12-17 years of age.

Methods: A single dose of 1000 mg of dalbavancin (the standard adult dose) was administered as a 30-minute intravenous infusion to subjects weighing 60 kg or greater and 15 mg/kg for subjects weighing <60 kg. A noncompartmental PK analysis was performed.

Results: The apparent terminal t1/2 was approximately 9 days and was similar for dalbavancin dosages of 1000 mg and 15 mg/kg. Median dalbavancin plasma exposures (Cmax and AUCinf) when administered as 1000 mg to subjects weighing 60 kg or greater were similar to those when dalbavancin was administered at 15 mg/kg to subjects weighing <60 kg and slightly lower than exposures in adults given 1000 mg in prior PK and treatment studies. Single dose dalbavancin was well tolerated.

Conclusions: Given dalbavancin exposures documented in children 12-17 years of age, and recognized dose proportionality, appropriate dosing can be modeled for pediatric phase 3 trials in acute bacterial skin and skin structure infections, to achieve the same exposure that is reported to be safe and effective in adults.