title: Population pharmacokinetics and pharmacodynamic evaluation of intravenous and enteral moxifloxacin in surgical intensive care unit patients.
abstract: OBJECTIVE
  To describe the plasma concentration-time profile of moxifloxacin after intravenous and enteral administration in intensive care unit (ICU) patients and to provide a pharmacodynamic (PD) evaluation with regard to pneumonia.
  
  
  METHODS
  Twenty-five adult patients from a cardiothoracic/mixed surgical ICU were enrolled. Moxifloxacin was given as a standard dose (400 mg once daily). Therapy was successfully switched to enteral administration on day 5 in 16 patients. A rich data sampling schedule was performed after intravenous (day 4) and enteral (day 8) administration. Moxifloxacin concentrations were analysed by HPLC. A population pharmacokinetic (PK) model was developed using NONMEM VII. Simulated concentration-time profiles were evaluated for their probability of attaining PK/PD target values relevant for community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP).
  
  
  RESULTS
  A linear-elimination two-compartment model described the data adequately. Parameter estimates (coefficient of variation of inter-individual variability) were: absorption rate constant, 1.09/h (135%); enteral bioavailability, 76% (20.0%); central volume of distribution, 55.6 L; peripheral volume of distribution, 59.6 L (15.3%); inter-compartmental clearance, 47.7 L/h; and clearance, 11.3 L/h (23.7%). Both intravenously and enterally administered standard-dose moxifloxacin reliably attained the PK/PD target values for pathogens with MICs ≤ 0.25 mg/L for CAP and ≤ 0.125 mg/L for HAP.
  
  
  CONCLUSIONS
  Drug exposure to moxifloxacin in ICU patients was more variable than in healthy volunteers. The standard dosing provides sufficient drug exposure for treatment of CAP but for HAP it does so only when a highly susceptible pathogen is present. Intravenous/enteral sequential therapy may be considered for cautiously selected cases in ICU patients.
authors: Department of Anesthesiology and Intensive Care, Charité University Hospital Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. martin.kees@charite.de
authors: Martin Georg
authors: MG
authors: Kees
authors: André
authors: A
authors: Schaeftlein
authors: Helene Anna
authors: HA
authors: Haeberle
authors: Frieder
authors: F
authors: Kees
authors: Charlotte
authors: C
authors: Kloft
authors: Alexandra
authors: A
authors: Heininger
mesh_terms: D018806:APACHE; D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D001372:Aza Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D003198:Computer Simulation; D003422:Critical Care; D016638:Critical Illness; D004750:Enteral Nutrition; D005260:Female; D005470:Fluorometry; D024841:Fluoroquinolones; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D011153:Population; D011804:Quinolines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D012121:Respiration, Artificial; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin
keywords: ICUs; antimicrobial therapy; bioavailability; fluoroquinolones; pneumonia; probability of target attainment