title: The pharmacokinetics of oxycodone and its metabolites following single oral doses of Remoxy®, an abuse-deterrent formulation of extended-release oxycodone, in patients with hepatic or renal impairment.
abstract: OBJECTIVE
  Remoxy® (Pain Therapeutics, Inc., Austin, TX) is an abuse-deterrent formulation of extended-release oxycodone. The effects of renal or hepatic impairment on the pharmacokinetics (PK) of single, oral doses of Remoxy 20 or 10 mg, respectively, were assessed in two phase 1 studies in subjects aged 18-80 years.
  
  
  METHODS
  PK parameters included maximum plasma concentration (C(max)) and area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC(0-t)), and extrapolated to infinity (AUCinf). Adverse events (AEs) were monitored.
  
  
  RESULTS
  Mean (SD) oxycodone Cmax values following Remoxy 20-mg administration were 17.6 (9.1), 21.9 (11.2), 25.9 (18.2), and 31.6 (14.5) ng/mL and AUC0-t values were 210.7 (82.1), 271.6 (83.3), 299.5 (76.3), and 493.5 (175.9) ng·h/mL in subjects with normal or mild (n = 6 each), moderate (n = 5), and severely impaired renal function (n = 6), respectively. Mean (SD) oxycodone Cmax following Remoxy 10-mg administration was 7.6 (3.3), 7.8 (2.3), and 13.1 (5.3) ng/mL and AUC(0-t) was 105.7 (49.5), 134.7 (38.3), and 218.0 (74.1) ng·h/mL in subjects with normal, mild, and moderately impaired hepatic function (n = 6 each), respectively. Differences in exposure values between the different renal and hepatic groups were significant. Treatment-emergent AEs were reported by 14.3, 66.7, 66.7, and 50.0 percent of subjects with normal, mild, moderate, and severely impaired renal function, respectively, and by 50.0, 33.3, and 66.7 percent of subjects with normal, mild, and moderately impaired hepatic function, respectively.
  
  
  CONCLUSIONS
  As renal or hepatic function decreased, oxycodone Cmax and AUC(0-t) were up to approximately twofold higher following single, oral doses of extended-release Remoxy. AEs were those typically reported for opioids. Lower doses of Remoxy may thus be safely prescribed to subjects with renal or hepatic impairment.
authors.affiliation: Senior Director, Pfizer Inc, New York, New York.
authors.forename: Bimal K
authors.initials: BK
authors.lastname: Malhotra
authors.affiliation: Chief Scientific Officer, Pain Therapeutics, Inc., Austin, Texas.
authors.forename: Grant L
authors.initials: GL
authors.lastname: Schoenhard
authors.affiliation: Pain Therapeutics, Inc., Austin, Texas.
authors.forename: Annelies W
authors.initials: AW
authors.lastname: de Kater
authors.affiliation: Chief Operating and Medical Officer, Pain Therapeutics, Inc., Austin, Texas.
authors.forename: Nadav
authors.initials: N
authors.lastname: Friedmann
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008107:Liver Diseases / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010098:Oxycodone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D051437:Renal Insufficiency / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D010098:Oxycodone