title: Pain management in chronic kidney disease: the pharmacokinetics and pharmacodynamics of hydromorphone and hydromorphone-3-glucuronide in hemodialysis patients.
abstract: OBJECTIVE
  To describe the pharmacokinetics of hydromorphone (HM) and its primary metabolite hydromorphone-3-glucuronide (H3G) both on and off dialysis in relation to the pharmacodynamic measurements of pain.
  
  
  METHODS
  Prospective, open-label, observational study.
  
  
  METHODS
  Canadian, university-based renal program.
  
  
  METHODS
  Twelve anuric hemodialysis patients with chronic pain, established on immediate-release HM.
  
  
  METHODS
  HM and H3G plasma concentrations were measured during and between hemodialysis treatments using a reverse-phase high-performance liquid chromatography assay with liquid chromatography/mass spectrometer/mass spectrometer detection. The McGill Pain Questionnaire (MPQ) and a Visual Analogue Scale (VAS) were used to measure pain. Noncompartmental analyses were conducted. Adverse effects were recorded.
  
  
  RESULTS
  HM did not substantially accumulate (accumulation factor R = 2.7 (1.6)), most likely due to the rapid conversion to H3G. Conversely, H3G accumulated between dialysis treatments (R = 12.5 (12.1)) but appeared to be effectively removed during hemodialysis (1.8 (0.7), p = 0.03). HM resulted in > 65 percent reduction in pain over dosing intervals. Mean MPQ pain scores decreased from 39.8 (18.2) to 12.3 (16.2) on dialysis and from 35.0 (18.5) to 15.5 (13.6) between dialysis treatments. Mean VAS pain scores decreased from 7.5 (2.5) to 3.0 (1.5) on dialysis and from 5.9 (3.2) to 4.4 (1.6) between dialysis treatments. No clinically significant opioid toxicity was observed. The accumulation of H3G between hemodialysis treatments was associated with greater sensory-type pain (r = 0.76, p < 0.0001) and reduced duration of analgesia.
  
  
  CONCLUSIONS
  HM may be a safe and effective opioid for use in selected hemodialysis patients.
authors.affiliation: Division of Nephrology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Sara N
authors.initials: SN
authors.lastname: Davison
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Mayo
mesh_terms: D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D002908:Chronic Disease; D005260:Female; D005965:Glucuronates / Q000097:blood*; D006207:Half-Life; D006801:Humans; D004091:Hydromorphone / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010146:Pain / Q000145:classification / Q000188:drug therapy* / Q000209:etiology; D011446:Prospective Studies; D006435:Renal Dialysis; D011795:Surveys and Questionnaires
chemical_list: D000701:Analgesics, Opioid; D005965:Glucuronates; C093624:hydromorphone-3-glucuronide; D004091:Hydromorphone