title: Pharmacodynamics of orally administered sustained- release hydromorphone in humans.
abstract: BACKGROUND
  The disposition kinetics of hydromorphone generally necessitates oral administration every 4 h of the conventional immediate-release tablet to provide sustained pain relief. This trial examined time course and magnitude of analgesia to experimental pain after administration of sustained-release hydromorphone as compared with that after immediate-release hydromorphone or placebo.
  
  
  METHODS
  Using a 4 x 4 Latin square double-blind design, 12 subjects were randomized to receive a single dose of 8, 16, and 32 mg sustained-release hydromorphone and placebo. The same subjects had received 8 mg immediate-release hydromorphone before this study. Using an electrical experimental pain paradigm, analgesic effects were assessed for up to 30 h after administration, and venous hydromorphone plasma concentrations were measured at corresponding times.
  
  
  RESULTS
  The hydromorphone plasma concentration peaked significantly later (12.0 h [12.0--18.0] vs. 0.8 h [0.8--1.0]; median and interquartile range) but was maintained significantly longer at greater than 50% of peak concentration (22.7 +/- 8.2 h vs. 1.1 +/- 0.7 h; mean +/- SD) after sustained-release than after immediate-release hydromorphone. Similarly, sustained-release hydromorphone produced analgesic effects that peaked significantly later (9.0 h [9.0--12.0] vs. 1.5 h [1.0--2.0]) but were maintained significantly longer at greater than 50% of peak analgesic effect (13.3 +/- 6.3 h vs. 3.6 +/- 1.7 h). A statistically significant linear relation between the hydromorphone plasma concentration and the analgesic effect on painful stimuli existed.
  
  
  CONCLUSIONS
  A single oral dose of a new sustained-release formulation of hydromorphone provided analgesia to experimental pain beyond 24 h of its administration.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, California 94305-5117, USA. ang@leland.stanford.edu
authors.forename: M S
authors.initials: MS
authors.lastname: Angst
authors.forename: D R
authors.initials: DR
authors.lastname: Drover
authors.forename: J
authors.initials: J
authors.lastname: Lötsch
authors.forename: B
authors.initials: B
authors.lastname: Ramaswamy
authors.forename: S
authors.initials: S
authors.lastname: Naidu
authors.forename: D R
authors.initials: DR
authors.lastname: Wada
authors.forename: D R
authors.initials: DR
authors.lastname: Stanski
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000698:Analgesia; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D016014:Linear Models; D008297:Male; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004091:Hydromorphone