title: Epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidural opioids (part 1): differences among opioids.
abstract: BACKGROUND
  The pharmacokinetics of epidurally administered drugs has been the subject of many studies, yet drug concentration in the epidural space has never been measured. This study was undertaken to characterize the epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidurally administered opioids on the basis of measurement of drug concentration in each of these compartments after epidural administration.
  
  
  METHODS
  Morphine plus alfentanil, fentanyl, or sufentanil were administered epidurally in anesthetized pigs. Microdialysis was used to sample the epidural space and the cerebrospinal fluid for measurement of opioid concentration over time. Plasma samples were obtained from the central venous plasma and the epidural venous plasma. These data were used to calculate relevant pharmacokinetic parameters, including mean residence time, elimination half-lives, areas under the concentration versus time curves, clearance, and volume of distribution for each opioid in each compartment.
  
  
  RESULTS
  Some of the more important findings were that the cerebrospinal fluid and plasma pharmacokinetics of the opioids did not parallel their epidural pharmacokinetics and that their hydrophobic character governed multiple aspects of their lumbar epidural pharmacokinetics.
  
  
  CONCLUSIONS
  The findings indicate that the spinal pharmacokinetics of these drugs are complex and, in some ways, counterintuitive. Also, the bioavailability of opioids in the cerebrospinal fluid and epidural space is determined primarily by their hydrophobicity, with less hydrophobic drugs having greater bioavailability.
authors.affiliation: Department of Anesthesiology, Box 356540, University of Washington, Seattle, Washington 98195, USA. chrisb@u.washington.edu
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Bernards
authors.forename: Danny D
authors.initials: DD
authors.lastname: Shen
authors.forename: Emily S
authors.initials: ES
authors.lastname: Sterling
authors.forename: Jason E
authors.initials: JE
authors.lastname: Adkins
authors.forename: Linda
authors.initials: L
authors.lastname: Risler
authors.forename: Brian
authors.initials: B
authors.lastname: Phillips
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Ummenhofer
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D015360:Analgesia, Epidural; D000701:Analgesics, Opioid / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004305:Dose-Response Relationship, Drug; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D008970:Molecular Weight; D012039:Regional Blood Flow / Q000502:physiology; D012995:Solubility; D012997:Solvents; D013116:Spinal Cord / Q000098:blood supply; D013552:Swine; D014018:Tissue Distribution
chemical_list: D000701:Analgesics, Opioid; D012997:Solvents