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Pharmacokinetics and behavioral effects of liposomal hydromorphone suitable for perioperative use in rhesus macaques

Pharmacokinetics and behavioral effects of liposomal hydromorphone suitable for perioperative use in rhesus macaques,10.1007/s00213-011-2239-y,Psychop

Pharmacokinetics and behavioral effects of liposomal hydromorphone suitable for perioperative use in rhesus macaques  
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Introduction  This study aims to evaluate the pharmacokinetic, behavioral, and motor effects of a liposomal preparation of hydromorphone hydrochloride (LE-hydro) in rhesus monkeys. We administered either 2 mg/kg of LE-hydro (n = 8) subcutaneous (s.c.) or 0.1 mg/kg of standard pharmaceutical hydromorphone HCl (hydro) preparation either intravenous (i.v.; n = 4) or s.c. (n = 5). Materials and methods  Serial blood samples were drawn after injection and analyzed for serum hydro concentration by liquid chromatography/mass spectrometry. Following s.c. injection of 0.1 mg/kg hydro or 2 mg/kg LE-hydro, behavioral evaluations were conducted in groups of rhesus monkeys (n = 10/group) in the presence of a compatible stimulus animal and motor skills were also evaluated (n = 10/group). The motor skills test consisted of removing a food reward (carrot ring) from either a straight peg (simple task) or a curved peg (difficult task). Results  LE-hydro (MRT0-INF = 105.9 h) demonstrated extended-release pharmacokinetics compared to hydro when administered by either i.v. (MRT0-INF =1.1 h) or s.c. (MRT0-INF =1.3 h) routes. Hydro did not affect motor performance of the simpler task, but the monkeys’ performance deteriorated on the more difficult task at 0.5 and 1 h after injection. LE-hydro had no effect on motor skills in either the simpler or more difficult task. Conclusions  The results of these studies indicate that LE-hydro has a pharmacokinetic and behavioral side effects profile consistent with an analgesic that could be tested for surgical use in animals. Our studies also expand the use of rhesus monkeys as a translational behavioral pharmacodynamics model for testing extended-release opioid medication.
Journal: Psychopharmacology , vol. 216, no. 4, pp. 511-523, 2011
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