title: Compartmental pharmacokinetics of nefopam during mild hypothermia.
abstract: BACKGROUND
  Nefopam is a non-opioid, non-steroidal, centrally acting analgesic which has an opioid-sparing effect. It also reduces the threshold (triggering core temperature) for shivering without causing sedation or respiratory depression. The drug is therefore useful as both an analgesic and to facilitate induction of therapeutic hypothermia. However, compartmental pharmacokinetics during hypothermia are lacking for nefopam.
  
  
  METHODS
  We conducted a prospective, randomized, blinded study in eight volunteers. On two different occasions, one of two nefopam concentrations was administered and more than 30 arterial blood samples were gathered during 12 h. Plasma concentrations were determined using gas chromatography/mass spectrometry to investigate the pharmacokinetics of nefopam with non-linear mixed-effect modelling.
  
  
  RESULTS
  A two-compartment mammillary model with moderate inter-individual variability and inter-occasional variability independent of covariates was found to best describe the data [mean (SE): V(1)=24.13 (2.8) litre; V(2)=183.34 (13.5) litre; Cl(el)=0.54 (0.07) litre min(-1); Cl(dist)=2.84 (0.42) litre min(-1)].
  
  
  CONCLUSIONS
  The compartmental data set describing a two-compartment model was determined and could be implemented to drive automated pumps. Thus, work load could be distributed to a pump establishing and maintaining any desired plasma concentration deemed necessary for a treatment with therapeutical hypothermia.
authors.affiliation: Department of Outcomes Research-E30, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. podrans@gmx.net
authors.forename: T
authors.initials: T
authors.lastname: Podranski
authors.forename: T W
authors.initials: TW
authors.lastname: Bouillon
authors.forename: T
authors.initials: T
authors.lastname: Riva
authors.forename: A M
authors.initials: AM
authors.lastname: Kurz
authors.forename: M J
authors.initials: MJ
authors.lastname: Oehmke
mesh_terms: D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D001833:Body Temperature Regulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D008954:Models, Biological; D009340:Nefopam / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D011446:Prospective Studies; D012768:Shivering / Q000187:drug effects; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D009340:Nefopam