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.
Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA. lisakh@rarc.wisc.edu
Lisa
L
Krugner-Higby
Butch
B
KuKanich
Brynn
B
Schmidt
Timothy D
TD
Heath
Carolyn
C
Brown
Lesley J
LJ
Smith
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