Pharmacokinetics and behavioral effects of an extended-release, liposome-encapsulated preparation of oxymorphone in rhesus macaques.
The objectives of the study were to determine the pharmacokinetics of oxymorphone (oxy) and of ammonium sulfate-loaded, liposome-encapsulated oxymorphone (LE-ASG oxy) and to evaluate the behavioral effects of both opioid preparations by using ethographic evaluation specific to rhesus monkeys. Rhesus monkeys (n = 8) were injected with 2.0 mg/kg LE-ASG oxy s.c.. Blood samples were collected at serial time points up to 144 h in six monkeys and up to 456 h in two monkeys. Separate groups of monkeys were injected with 0.1 mg/kg oxy s.c. (n = 4) or i.v. (n = 5). Blood samples were collected at serial time points up to 24 h after injection. Pharmacokinetic parameters were calculated by using commercially available software. Behavior was recorded in a different group of 10 monkeys administered LE-ASG oxy (2.0 mg/kg s.c.) or oxy (0.1 mg/kg s.c.) on separate occasions. Behavioral evaluations were made at serial time points while monkeys were in an extended cage with a compatible stimulus animal. Oxymorphone was rapidly eliminated from the serum in the oxy group. Measurable drug was present in serum for up to 4 h after oxy was administered subcutaneously or intravenously. LE-ASG oxy was present in serum in measurable concentrations for more than 2 weeks. Neither oxy nor LE-ASG oxy produced observable sedation. LE-ASG oxy decreased some environmentally directed behaviors, but this drug formulation increased watchfulness, decreased self-directed and elimination behaviors, increased nonspecific social contact, and decreased threat behaviors. LE-ASG oxy persisted for an extended period in rhesus monkey serum and produced behavioral changes consistent with this opioid.
Krugner-Higby
Lisa
L
Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA. lisakh@rarc.wisc.edu
KuKanich
Butch
B
Schmidt
Brynn
B
Heath
Timothy D
TD
Brown
Carolyn
C
Smith
Lesley J
LJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D002214:Capsules; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D008081:Liposomes / Q000493:pharmacokinetics; D008253:Macaca mulatta; D008297:Male; D010111:Oxymorphone / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D002214:Capsules; D003692:Delayed-Action Preparations; D008081:Liposomes; D010111:Oxymorphone