title: Pharmacokinetics of hydromorphone after intravenous and intramuscular administration in male rhesus macaques (Macaca mulatta).
abstract: This study reports the pharmacokinetics of hydromorphone after intravenous and intramuscular administration to rhesus macaques (Macaca mulatta). Hydromorphone (0.075 mg/kg) was administered intravenously as a bolus or intramuscularly on separate occasions to healthy, socially housed, socially reared, adult, intact male rhesus macaques (n = 4). Blood samples were collected prior to and until 10 h after administration. Serum hydromorphone concentrations were analyzed with liquid chromatography-mass spectrometry. Compartment models were fit to time-concentration data. A 3-compartment model with input in and elimination from the central compartment best fit intravenous data, whereas a 1-comparment model best fit intramuscular data. After intravenous administration, the median clearance and terminal half-life were 37.7 (range, 33.7 to 47.1) mL/kg/min and 142 (range, 131 to 218) min, respectively. The median (range) elimination half-life after intramuscular administration was 81.5 (77.2 to 92.5) min. Median intramuscular bioavailability was 92% (range, 75% to 104%). Rhesus macaques maintained concentrations greater than or equal to 4.0 ng/mL for at least 2 h after intravenous and intramuscular administration. The disposition of hydromorphone was characterized by a large volume of distribution and moderate clearance. Intramuscular administration resulted in rapid and almost complete drug absorption. Whole-body pruritus, sedation, and decreased appetite were observed in all macaques after initial drug administration.
authors.affiliation: Department of Primate Medicine, California National Primate Research Center, Davis, California, USA krskelly@ucdavis.edu.
authors.forename: Kristi R
authors.initials: KR
authors.lastname: Kelly
authors.affiliation: Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Pypendop
authors.affiliation: Department of Primate Medicine, California National Primate Research Center, Davis, California, USA; Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
authors.forename: Kari L
authors.initials: KL
authors.lastname: Christe
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D006207:Half-Life; D004091:Hydromorphone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007700:Kinetics; D008253:Macaca mulatta; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000662:veterinary*
chemical_list: D000701:Analgesics, Opioid; D004091:Hydromorphone