Single-dose Pharmacokinetics of Daptomycin in Pediatric Patients 3–24 Months of Age

Abstract

To match known clinically and microbiologically effective exposures in adults, infants require higher mg/kg daptomycin doses. Daptomycin safety and efficacy have not been established in pediatric patients. Pediatric clinical trials are ongoing.

Daptomycin for Complicated Skin Infections: A Randomized Trial

“…Daptomycin clearance and the volume of distribution in these children were found to increase with decreasing age, which is consistent with previous reports. [19][20][21] The daptomycin doses selected for each age group achieved exposures similar to those in adults and were validated as safe and effective. At test-of-cure, there were only 2 confirmed clinical failures and 2 microbiological failures.…”

Development of Human Membrane Transporters: Drug Disposition and Pharmacogenetics

“…Renal clearance of digoxin in young children may be more dependent on ABCB1-mediated tubular secretion than in adults [ 39 ] Tacrolimus ABCB1 PGx studies of ABCB1 in relation to tacrolimus PKs appear contradictory [ 42 , 43 , 46 , 47 ]. In pediatric liver transplant recipients, high intestinal ABCB1 mRNA expression was associated with a twofold higher tacrolimus clearance [ 48 ] Daptomycin ABCB1 Higher body size-corrected renal daptomycin clearance in neonates and younger infants [ 51 – 53 ] Fexofenadine OATP2B1, ABCB1, MRP2 Apparent bodyweight-corrected oral clearance was 1.5-fold lower in children 6 months to 6 years than in children 6–12 years [ 58 ] Morphine OCT1, ABCB1, ABCC2, ABCC3, OATP1B1 Neonates and infants have low morphine clearance in the first 10 days of life, increasing thereafter, largely due to immature UGT2B7 metabolism, but transporters may contribute [ 64 , 65 ]. Neonates are more prone to morphine-related respiratory depression [ 66 ].…”

The Use of Daptomycin to Treat Methicillin-Resistant Staphylococcus Epidermidis Bacteremia in a Critically Ill Child with Renal Failure

“…6 Reports of experience with daptomycin use in infants and children are limited. [7][8][9][10][11][12][13][14][15][16][17] There is marked variation in dosage regimens between these studies with IV doses of 4-12 mg/kg and intervals of 12 and 24 hours described for a wide range of indications including cellulitis, osteomyelitis, meningitis, bacteremia, and endocarditis. Daptomycin efficacy is concentrationdependent and related to area under the concentration-time curve (AUC)/MIC and maximum plasma daptomycin concentration-to-MIC ratios.…”