Pharmacokinetics of Colistin Following a Single Dose of Intravenous Colistimethate Sodium in Critically Ill Neonates

In this study, we sought to evaluate the pharmacokinetics of colistin after intravenous administration of colistimethate sodium (CMS) in the critically ill neonates with Gram-negative bacterial infections. A single intravenous dose of CMS [approximately 150,000 IU/kg, equivalent to 5 mg/kg colistin base activity (CBA)] was administered to 7 critically ill neonates. Mean (+/- SD) maximum plasma colistin concentration and area under the time-concentration curve from 0 to infinity were 3.0 +/- 0.7 mu g/mL and 25.3 +/- 10.4 mu g . h/mL, respectively. Time to maximum concentration, half-life, apparent volume of distribution and clearance were 1.3 +/- 0.9 hours, 9.0 +/- 6.5 hours, 7.7 +/- 9.3 L/kg and 0.6 +/- 0.3 L/h/kg, respectively. After a dose regimen of 5 mg/kg CBA every 24 hours, the average concentration expected at steady state is 1.1 +/- 0.4 mu g/mL. In critically ill neonates, a single intravenous dose of 5 mg CBA/kg (approximately 150,000 IU/kg of CMS) resulted in suboptimal plasma concentrations of colistin. According to our pharmacokinetics data, the dosage of CMS currently used in critically ill neonates is insufficient.