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Pharmacokinetics of hydromorphone hydrochloride after intravenous and intramuscular administration in guinea pigs (Cavia porcellus)

Barbara Ambros DVM, MVetSc1, Heather K. Knych DVM, PhD2, and Miranda J. Sadar DVM3
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  • 1 1Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, Saskatoon, SK S7N 5B4, Canada.
  • | 2 2Department of Molecular Biosciences and the K.L. Maddy Equine Analytical Chemistry Laboratory, University of California-Davis, Davis, CA 95616.
  • | 3 3Department of Clinical Sciences, Veterinary Teaching Hospital, College of Veterinary Medicine and Biomedical Sciences, Fort Collins, CO 80523.

Abstract

OBJECTIVE

To determine the pharmacokinetics of hydromorphone hydrochloride after IV and IM administration in guinea pigs (Cavia porcellus).

ANIMALS

8 healthy adult guinea pigs (4 sexually intact females and 4 sexually intact males).

PROCEDURES

In a crossover study, hydromorphone (0.3 mg/kg) was administered once IM (epaxial musculature) or IV (cephalic catheter) to each guinea pig at a 1-week interval (2 treatments/guinea pig). Blood samples were collected before and at predetermined intervals after drug administration via a vascular access port. Plasma hydromorphone concentrations were determined by liquid chromatography–tandem mass spectrometry. Noncompartmental analysis of data was used to calculate pharmacokinetic parameters.

RESULTS

Mean ± SD clearance and volume of distribution for hydromorphone administered IV were 52.8 ± 13.5 mL/min/kg and 2.39 ± 0.479 L/kg, respectively. Mean residence time determined for the IV and IM administration routes was 0.77 ± 0.14 hours and 0.99 ± 0.34 hours, respectively. The maximum observed plasma concentration following IM administration of hydromorphone was 171.9 ± 29.4 ng/mL. No sedative effects were observed after drug administration by either route.

CONCLUSIONS AND CLINICAL RELEVANCE

Pharmacokinetic data indicated that hydromorphone at a dose of 0.3 mg/kg may be administered IV every 2 to 3 hours or IM every 4 to 5 hours to maintain a target plasma concentration between 2 and 4 ng/mL in guinea pigs. Hydromorphone had high bioavailability after IM administration. Further research is necessary to evaluate the effects of other doses and administration routes and the analgesic effects of hydromorphone in guinea pigs.

Contributor Notes

Address correspondence to Dr. Ambros (barbara.ambros@usask.ca).