title: Serum and cerebrospinal fluid concentrations of midazolam after epidural administration in dogs.
abstract: The epidural administration of midazolam has analgesic effects that might be mediated by gamma-aminobutyric acid type A receptors in the spinal cord. In this study, we examined both serum and cerebrospinal fluid (CSF) concentrations of midazolam after epidural administration to investigate the possibility of midazolam entering CSF directly from the epidural space. Five male mongrel dogs had catheters inserted in a femoral artery, the epidural space at L3-4, and the intrathecal space at the atlanto-occipital region under general anesthesia. Midazolam 1 mg/kg was epidurally administered, and arterial blood and CSF samples were collected until 240 min after the midazolam administration to measure midazolam concentration. Serum midazolam concentration increased and reached a peak at 30 min after the administration (224.8 +/- 30.5 ng/mL) and then decreased to 25.8 +/- 6.0 ng/mL at 240 min. Midazolam concentration in the CSF was less than the detection limit at 5 min, reached a peak at 30 min after the administration (7.2 +/- 4.7 ng/mL), and decreased to 3.6 +/- 3.3 ng/mL at 240 min. In conclusion, epidurally administered midazolam enters CSF, but CSF concentrations are only 3% of those in the systemic circulation.
  
  
  CONCLUSIONS
  Midazolam, which has spinally mediated analgesic potency, was epidurally administered in dogs, and serum and cerebrospinal fluid concentrations were measured. Epidurally administered midazolam enters the cerebrospinal fluid, but concentrations are only 3% of those in the systemic circulation.
authors.affiliation: Department of Anesthesiology, The University of Tokyo, Japan. nishiyamat-ane@h.u-tokyo.ac.jp
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nishiyama
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Tamai
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hanaoka
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D002404:Catheterization; D004285:Dogs; D004824:Epidural Space / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007268:Injections, Epidural; D008297:Male; D008874:Midazolam / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*
chemical_list: D014151:Anti-Anxiety Agents; D008874:Midazolam