Comparison of the pharmacokinetics of oxycodone and noroxycodone in male dark agouti and Sprague-Dawley rats: Influence of streptozotocin-induced diabetes

Huang, L., Edwards, S. R. and Smith, M. T. (2005) Comparison of the pharmacokinetics of oxycodone and noroxycodone in male dark agouti and Sprague-Dawley rats: Influence of streptozotocin-induced diabetes. Pharmaceutical Research, 22 9: 1489-1498. doi:10.1007/s11095-005-6154-y


Author Huang, L.
Edwards, S. R.
Smith, M. T.
Title Comparison of the pharmacokinetics of oxycodone and noroxycodone in male dark agouti and Sprague-Dawley rats: Influence of streptozotocin-induced diabetes
Journal name Pharmaceutical Research   Check publisher's open access policy
ISSN 0724-8741
Publication date 2005-01-01
Year available 2005
Sub-type Article (original research)
DOI 10.1007/s11095-005-6154-y
Open Access Status Not yet assessed
Volume 22
Issue 9
Start page 1489
End page 1498
Total pages 10
Editor V. H. L. Lee
Place of publication USA
Publisher Springer New York
Language eng
Subject C1
320501 Pharmaceutical Sciences and Pharmacy
730104 Nervous system and disorders
1115 Pharmacology and Pharmaceutical Sciences
1109 Neurosciences
Abstract Purpose. The aims of this study are to evaluate whether cytochrome P450 (CYP)2D1/2D2-deficient dark agouti (DA) rats and/or CYP2D1/2D2-replete Sprague-Dawley (SD) rats are suitable preclinical models of the human, with respect to mirroring the very low plasma concentrations of metabolically derived oxymorphone seen in humans following oxycodone administration, and to examine the effects of streptozotocin-induced diabetes on the pharmacokinetics of oxycodone and its metabolites, noroxycodone and oxymorphone, in both rodent strains. Methods. High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was used to quantify the serum concentrations of oxycodone, noroxycodone, and oxymorphone following subcutaneous administration of bolus doses of oxycodone (2 mg/kg) to groups of nondiabetic and diabetic rats. Results. The mean (+/- SEM) areas under the serum concentration vs. time curves for oxycodone and noroxycodone were significantly higher in DA relative to SD rats (diabetic, p < 0.05; nondiabetic, p < 0.005). Serum concentrations of oxymorphone were very low (< 6.9 nM). Conclusions. Both DA and SD rats are suitable rodent models to study oxycodone's pharmacology, as their systemic exposure to metabolically derived oxymorphone (potent mu-opioid agonist) is very low, mirroring that seen in humans following oxycodone administration. Systemic exposure to oxycodone and noroxycodone was consistently higher for DA than for SD rats showing that strain differences predominated over diabetes status.
Keyword Chemistry, Multidisciplinary
Pharmacology & Pharmacy
Diabetes
Metabolism
Oxycodone
Pharmacokinetics
Rat
Controlled-release Oxycodone
Randomized Controlled-trial
Inbred Mouse Strains
Opioid Analgesia
Spinal-cord
Morphine
Pain
Antinociception
Neuropathy
Cancer
Q-Index Code C1
Institutional Status UQ

 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 16 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 13 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 15 Aug 2007, 15:49:34 EST