The activity of Oxycodone Hydrochloride Oral Solution is primarily due to the parent drug oxycodone.

Absorption: The oral bioavailability of oxycodone is 60% to 87%. This high oral bioavailability (compared to other oral opioids) is due to lower pre-systemic and/or first-pass metabolism of oxycodone. 

Food Effect: Presence of food may slightly delay the rate (C max and T max) and enhance the extent of absorption (AUC) of oxycodone from Oxycodone Hydrochloride Oral Solution. Overall, food is not expected to have a clinically significant impact on the absorption of Oxycodone Hydrochloride Oral Solution. 

Distribution: Following intravenous administration, the volume of distribution (Vss) for oxycodone was 2.6 L/kg. Plasma protein binding of oxycodone at 37°C and a pH of 7.4 was about 45%. Oxycodone has been found in breast milk [see Use in Specific Populations (8.2)]. 

Elimination:Metabolism: Oxycodone hydrochloride is extensively metabolized to noroxycodone, oxymorphone, noroxymorphone, which are subsequently glucuronidated. CYP3A4 mediated N-demethylation to noroxycodone is the primary metabolic pathway of oxycodone with a less contribution from CYP2D6 mediated O-demethylation to oxymorphone. Therefore, the formation of these and related metabolites can, in theory, be affected by other drugs. The major circulating metabolite is noroxycodone with an AUC ratio of 0.6 relative to that of oxycodone. Noroxycodone is reported to be a considerably weaker analgesic than oxycodone. Oxymorphone, although possessing analgesic activity, is present in the plasma only in low concentrations. The correlation between oxymorphone concentrations and opioid effects was much less than that seen with oxycodone plasma concentrations. The analgesic activity profile of other metabolites is not known. 

Excretion: Oxycodone and its metabolites are excreted primarily via the kidney. The amounts measured in the urine have been reported as follows: free oxycodone up to 19%; conjugated oxycodone up to 50%; free oxymorphone 0%; conjugated oxymorphone ≤ 14%; both free and conjugated noroxycodone have been found in the urine but not quantified. The total plasma clearance was 0.8 L/min for adults. Apparent elimination half-life of oxycodone following the administration of Oxycodone Hydrochloride Oral Solution was approximately 3.5 hours. 

Special Populations:Age: Geriatric Population:Information obtained from oxycodone tablets indicate that the plasma concentrations of oxycodone did not appear to be increased in patients over of the age of 65. 

Hepatic Impairment: Because oxycodone is extensively metabolized in the liver, its clearance may decrease in hepatic-impaired patients. A dose adjustment is recommended in these patients [see Use in Special Populations (8.6)]. 

Renal Impairment: Because this drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function, a dose reduction is recommended for renal impaired patients [see Use in Special Populations (8.7)]. 

Drug Interactions Studies:CYP3A4 Inhibitors: CYP3A4 is the major enzyme involved in noroxycodone formation. A published study showed that the co-administration of voriconazole, a CYP3A4 inhibitor, increased oxycodone AUC and C max by 3.6 and 1.7 fold, respectively. 

CYP3A4 Inducers: A published study showed that the co-administration of rifampin, a drug metabolizing enzyme inducer, decreased oxycodone AUC and C max values by 86% and 63%, respectively. 

CYP2D6 Inhibitors: Oxycodone is metabolized in part to oxymorphone via the cytochrome p450 isoenzyme CYP2D6. While this pathway may be blocked by a variety of drugs (e.g., certain cardiovascular drugs and antidepressants), such blockade has not yet been shown to be of clinical significance with this agent.