title: Pulmonary and Systemic Pharmacokinetics of Colistin Following a Single Dose of Nebulized Colistimethate in Mechanically Ventilated Neonates.
abstract: The purpose of this study was to evaluate the pulmonary and systemic pharmacokinetics of colistin following a single dose of nebulized colistimethate sodium (CMS) in mechanically ventilated neonates. We administered a single dose of nebulized CMS (approximately 120,000 IU/kg of CMS, equivalent to 4 mg/kg colistin base activity) to 6 ventilated neonates with ventilator-associated pneumonia. The median gestational age was 39 weeks (range, 32-39 weeks). Mean (± SD) tracheal aspirate colistin maximum concentration (Cmax), area under the concentration-time curve (AUC 0-24) and t1/2 were 24.0 ± 8.2 μg/mL, 147.6 ± 53.5 μg · hours/mL and 9.8 ± 5.5 hours, respectively. The plasma concentrations of colistin were low. In neonates, a single nebulized dose of CMS (120,000 IU) resulted in high local concentrations for at least 12 hours and low systemic concentrations of colistin. Twice daily nebulization might be more appropriate.
authors.affiliation: From the *Department of Pediatrics, Hat Yai Medical Education Center, Hat Yai Hospital, Songkhla, Thailand; †Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; ‡Clinical and Experimental Pharmacokinetics Unit, and §Phase I Clinical Trial Unit and Experimental Therapy, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Narongsak
authors.initials: N
authors.lastname: Nakwan
authors.forename: Pichaya
authors.initials: P
authors.lastname: Lertpichaluk
authors.forename: Kulkanya
authors.initials: K
authors.lastname: Chokephaibulkit
authors.forename: Paola
authors.initials: P
authors.lastname: Villani
authors.forename: Mario
authors.initials: M
authors.lastname: Regazzi
authors.forename: Roberto
authors.initials: R
authors.lastname: Imberti
mesh_terms: D000280:Administration, Inhalation; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D003091:Colistin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010949:Plasma / Q000737:chemistry*; D011446:Prospective Studies; D012121:Respiration, Artificial; D013997:Time Factors; D014132:Trachea / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; C004691:colistinmethanesulfonic acid; D003091:Colistin