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

• Published in: Pharmaceutical research 2005-09, Vol.22 (9), p.1489-1498
• Main Authors: Huang, Lillian, Edwards, Stephen R, Smith, Maree T
• Format: Article
• Language: English
• Subjects: Alcohol Oxidoreductases - genetics; Alcohol Oxidoreductases - metabolism; Analgesics, Opioid - pharmacokinetics; Animals; Aryl Hydrocarbon Hydroxylases - genetics; Aryl Hydrocarbon Hydroxylases - metabolism; Chromatography, High Pressure Liquid; Cytochrome P450 Family 2; Diabetes Mellitus, Experimental - metabolism; Male; Morphinans - pharmacokinetics; Oxycodone - pharmacokinetics; Rats; Rats, Sprague-Dawley; Species Specificity; Spectrometry, Mass, Electrospray Ionization; Streptozocin
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-005-6154-y

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. 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. 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