title: Pharmacokinetics of single-dose daptomycin in patients with suspected or confirmed neurological infections.
abstract: There are currently few or no published data on the amount of cerebrospinal fluid (CSF) penetration of daptomycin in patients with suspected or documented neurosurgical infections. We conducted a prospective study, assessing the pharmacokinetics and CSF penetration of a single intravenous daptomycin dose administered at 10 mg/kg, based on total body weight (TBW), in six neurosurgical patients with indwelling external CSF shunts with suspected or documented meningitis or ventriculitis. Each patient had four blood and CSF samples drawn simultaneously at specific times after the end of infusion: 30 min, 6 h, 12 h, and 24 h. Pharmacokinetic parameters of daptomycin in serum were calculated using standard noncompartmental methods, and daptomycin was assayed using high-performance liquid chromatography (for serum) or liquid chromatography with mass spectrometry (for CSF). The mean (± standard deviation [SD]) maximum measured daptomycin concentrations were 93.7 ± 17.3 mg/liter in serum at 0.5 h postinfusion and 0.461 ± 0.51 mg/liter in CSF at 6 h postinfusion. The mean (± SD) daptomycin minimum concentrations were 13.8 ± 4.8 mg/liter in serum at 24 h postinfusion and 0.126 ± 0.12 mg/liter in CSF at 0.5 h postinfusion. The mean daptomycin penetration, determined by the area under the concentration-time curve in CSF (AUC(CSF))/(AUC(serum) ratio), was 0.8%. Corrected for protein binding, the overall CSF penetration was 11.5%. Additional pharmacokinetic studies evaluating multiple and/or higher dosages of daptomycin are necessary in human subjects to better characterize the CSF penetration of daptomycin in neurosurgical patients.
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan 48201, USA.
authors.forename: Ravina
authors.initials: R
authors.lastname: Kullar
authors.forename: Judy N
authors.initials: JN
authors.lastname: Chin
authors.forename: David J
authors.initials: DJ
authors.lastname: Edwards
authors.forename: Dennis
authors.initials: D
authors.lastname: Parker
authors.forename: William M
authors.initials: WM
authors.lastname: Coplin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rybak
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D020806:Central Nervous System Bacterial Infections / Q000097:blood / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D017576:Daptomycin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009493:Neurosurgery; D011446:Prospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin