title: Pharmacokinetics of ammonium sulfate gradient loaded liposome-encapsulated oxymorphone and hydromorphone in healthy dogs.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics, in dogs, of liposome-encapsulated oxymorphone and hydromorphone made by the ammonium sulfate gradient loading technique (ASG).
  
  
  METHODS
  Four healthy purpose-bred Beagles aged 9.5 ± 3.2 months and weighing 13.4 ± 2.3 kg.
  
  
  METHODS
  Randomized cross-over design.
  
  
  METHODS
  Each dog was given either 4.0 mg kg(-1) of ASG-oxymorphone or 8.0 mg kg(-1) of ASG-hydromorphone SC on separate occasions with a 3-month washout period. Blood was collected at baseline and at serial time points up to 1032 hours (43 days) after injection for determination of serum opioid concentrations. Serum opioid concentrations were measured with HPLC-MS and pharmacokinetic parameters were calculated using commercial software and non-compartmental methods.
  
  
  RESULTS
  Serum concentrations of oxymorphone remained above the limit of quantification for 21 days, while those for hydromorphone remained above the limit of quantification for 29 days. Cmax for ASG-oxymorphone was 7.5 ng mL(-1) ; Cmax for ASG-hydromorphone was 5.7 ng mL(-1) .
  
  
  CONCLUSIONS
  Oxymorphone and hydromorphone, when encapsulated into liposomes using the ammonium sulfate gradient loading technique, result in measureable serum concentrations for between 3 to 4 weeks. This formulation may have promise in the convenient use of opioids for clinical treatment of chronically painful conditions in dogs.
authors.affiliation: Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive, Madison WI 53706, USA. smithl@svm.vetmed.wisc.edu
authors.forename: Lesley J
authors.initials: LJ
authors.lastname: Smith
authors.forename: Butch K
authors.initials: BK
authors.lastname: Kukanich
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Krugner-Higby
authors.forename: Brynn H
authors.initials: BH
authors.lastname: Schmidt
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Heath
mesh_terms: D000645:Ammonium Sulfate / Q000737:chemistry*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D004285:Dogs / Q000097:blood*; D006207:Half-Life; D004091:Hydromorphone / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008081:Liposomes; D008297:Male; D010111:Oxymorphone / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000701:Analgesics, Opioid; D008081:Liposomes; D010111:Oxymorphone; D004091:Hydromorphone; D000645:Ammonium Sulfate
keywords: dog; hydromorphone; opioids; oxymorphone; pain management