Abstract. The ongoing epidemic of prescription opioid abuse in the United States has prompted interest in semi-synthetic opioids in the federal workplace drug testing program. This study characterized the metabolism and disposition of oxycodone (OC) in human urine. Twelve healthy adults were.
During the first collection period (0–2 h) following drug administration, creatinine and specific gravity averaged 21.8 mg/dL (11.2–60.7) and 1.0033 (1.0021–1.0067), respectively. During the ensuing time after drug administration, creatinine and specific gravity gradually rose and/or exceeded BL measures. During the second collection period (2–4 h), creatinine and specific gravity averaged 55.2 mg/dL (12.9–206.7) and 1.0064 (1.0021–1.0171), respectively. BL (pre-dose) measures (range) of creatinine and specific gravity averaged 87.4 mg/dL (19.9–221.8) and 1.0096 (1.0033–1.0212), respectively.
The percentage of specimens positive for OC in hydrolyzed urine at higher cutoff concentrations was as follows: 100 ng/mL, 64.2%; 150 ng/mL, 56.2%; 300 ng/mL, 45.3%; 500 ng/mL, 30.7%; 1,000 ng/mL, 13.1%; and 2,000 ng/mL, 5.1%.
Because the CYP3A4 isoenzyme plays a major role in the metabolism of oxycodone, drugs that inhibit CYP3A4 activity may cause decreased clearance of oxycodone which could lead to an increase in oxycodone plasma concentrations and result in increased or prolonged opioid effects. These effects could be more.
Skin and subcutaneous tissue disorders : dry skin, exfoliative dermatitis.
General disorders and administration site conditions : withdrawal syndrome (with and without seizures), edema, peripheral edema, thirst, malaise, chest pain, facial edema.
Gastrointestinal disorders : abdominal pain, diarrhea, dyspepsia, gastritis.
Close monitoring is of particular importance when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure.
Oxycodone is extensively metabolized; only 10% of dose is excreted unchanged in urine (Poyhia et al., 1991; Kirvela et al., 1996). The known metabolic scheme of oxycodone is presented in Fig. 1. Oxymorphone, a 3-O-demethylation metabolite of oxycodone, is a potent opioid that has a 3 to 5 times higher.
To further define the saturation kinetics of oxymorphone and noroxycodone formation from oxycodone, as well as noroxymorphone from either oxymorphone or noroxycodone, incubations were performed over the substrate range of 1 to 750 μM in Supersomes expressing CYP3A4, 3A5, and 2D6*1, either with or without supplementation of cytochrome b 5 (i.e., at 3:1 molar ratio of cytochrome b 5 to P450).
A fractional standard deviation error model (10%) was applied to the fits based on known analytical errors.
68 Oxycodone is a prodrug that undergoes hepatic metabolism via the CYP2D6 isoenzyme, whereby it is converted into its active metabolite oxymorphone, a µ-opioid agonist, and its inactive metabolite noroxycodone. Oxymorphone is reportedly often undetectable and is 14 times more potent than the parent compound.
This variation explains why some patients require higher than usual doses of oxycodone to achieve analgesia. Similar to codeine, there is genetic polymorphism in 10% of the population, which accounts for significant variation in the metabolism of oxycodone. Such interacting medications include neuroleptics, tricyclic antidepressants, and selective serotonin reuptake inhibitors (SSRIs). 81,82 Read full chapter. Cases of serotonin syndrome have been described in the literature when SSRIs and oxycodone were used concomitantly.
Noroxymorphone is a secondary metabolite of oxycodone formed mainly after O-demethylation of noroxycodone (mainly catalyzed by CYP2D6) and at a lower rate after N-demethylation of oxymorphone (mainly catalyzed by CYP3A4 and 2D6). The oxycodone and metabolites are excreted primarily via the kidneys.
In vivo metabolism can result in the conversion of a poor analgesic to a potent analgesic metabolite by revealing functional groups that allow high-affinity binding to opioid receptors as for example conversion of codeine to morphine and oxycodone to oxymorphone.9 Recent studies report the activation of the CNS toll-like receptor 4 (TLR4) signaling by diverse opioid structures which reflects an innate immune system response to xenobiotics.9,10. With the cloning of these receptors as well as the generation of selective antibodies for each of the receptors, it was possible to map their distribution in the central nervous system.