title: The disposition and cerebrospinal fluid penetration of morphine and its two major glucuronidated metabolites in adults undergoing lumbar myelogram.
abstract: OBJECTIVE
  To determine the pharmacokinetic disposition of morphine and its two major glucuronidated metabolites, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G), in serum and their penetration into cerebrospinal fluid (CSF).
  
  
  METHODS
  A single-dose, open-label pharmacokinetic study.
  
  
  METHODS
  The Memphis Neurosciences Center at Methodist Hospital.
  
  
  METHODS
  Twenty patients undergoing a diagnostic lumbar myelogram.
  
  
  METHODS
  All patients received morphine sulfate 10 mg intramuscularly approximately 1.5 hours before the procedure.
  
  
  RESULTS
  Three blood samples were drawn after the dose and a CSF sample was drawn immediately after lumbar puncture. The mean +/- standard deviation for the half-life of morphine was 2.8 +/- 1.4 hours. The apparent half-lives of M6G and M3G were 5.7 +/- 3.1 and 6.3 +/- 2.2 hours, respectively, and were inversely related to the estimated creatinine clearance (r = -0.61, p < 0.007 and r = -0.69, p < 0.002, respectively). The mean concentrations of morphine, M6G, and M3G in the CSF (collection time 1.5 +/- 0.32 hrs, n = 19) were 3.1 +/- 3.7, 12.5 +/- 17.6, and 19.6 +/- 16.1 nmol/L, respectively.
  
  
  CONCLUSIONS
  Elderly patients and patients with renal dysfunction receiving morphine may experience prolonged analgesic and adverse effects secondary to a decrease in the clearance of M6G.
authors.affiliation: Department of Clinical Pharmacy, University of Tennessee, Memphis 38163.
authors.forename: S C
authors.initials: SC
authors.lastname: Laizure
authors.forename: J H
authors.initials: JH
authors.lastname: Miller
authors.forename: R C
authors.initials: RC
authors.lastname: Stevens
authors.forename: D J
authors.initials: DJ
authors.lastname: Donahue
authors.forename: R E
authors.initials: RE
authors.lastname: Laster
authors.forename: D
authors.initials: D
authors.lastname: Brown
mesh_terms: D000328:Adult; D005260:Female; D006207:Half-Life; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D009022:Morphine Derivatives / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D009192:Myelography; D013129:Spinal Puncture
chemical_list: D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide