Single dose pharmacokinetics of linezolid in infants and children

Background. Linezolid is an oxazolidinone antibiotic with excellent in vitr o activity against a number of Gram-positive organisms including antibiotic -resistant isolates. The safety and pharmacokinetics of intravenously admin istered linezolid were evaluated in children and adolescents to examine the potential for developmental dependence on its disposition characteristics. Methods. Fifty-eight children (3 months to 16 years old) participated in th is study; 44 received a single 1.5-mg/kg dose and 14 received a single 10-m g/kg dose of linezolid administered by intravenous infusion. Repeated blood samples (n = 10 in children greater than or equal to 12 months; n = 8 in c hildren 3 to 12 months) were obtained during 24 h after drug administration , and linezolid was quantitated from plasma by high performance liquid chro matography with mass spectrometry detection. Plasma concentration us, time data were evaluated with a model independent approach. Results. Linezolid was web-tolerated by all subjects. The disposition of li nezolid appears to be age-dependent. A significant although weak correlatio n between age and total body clearance was observed. The mean (+/-SD) value s for elimination half-life, total clearance and apparent volume of distrib ution were 3.0 +/- 1.1 h, 0.34 +/- 0.15 liter/h/kg and 0.73 +/- 0.18 liter/ kg, respectively. Estimates of total body clearance and volume of distribut ion were significantly greater in children than historical values of adult data. As such maximum achievable linezolid plasma concentrations were sligh tly lower in children, and concentrations 12 h after a single 10-mg/kg dose were below the MTC,, for selected pathogens with in vitro susceptibility t o the drug. Conclusion. Based on these data a linezolid dose of 10 mg/kg given two to t hree times daily would appear appropriate for use in pediatric therapeutic clinical trials of this agent.