Oxycontin - Clinical Pharmacology

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Oxycodone is extensively metabolized and eliminated primarily in the urine as both conjugated and unconjugated metabolites. The apparent elimination half-life of oxycodone following the administration of OxyContin ® was 4.5 hours compared to 3.2 hours for immediate-release oxycodone.

Absorption

About 60% to 87% of an oral dose of oxycodone reaches the central compartment in comparison to a parenteral dose. This high oral bioavailability is due to low pre-systemic and/ or first-pass metabolism. In normal volunteers, the t½ of absorption is 0.4 hours for immediate-release oral oxycodone. In contrast, OxyContin Tablets exhibit a biphasic absorption pattern with two apparent absorption half-lives of 0.6 and 6.9 hours, which describes the initial release of oxycodone from the tablet followed by a prolonged release.

Plasma Oxycodone by Time Dose proportionality has been established for the 10 mg, 20 mg, 40 mg, and 80 mg tablet strengths for both peak plasma concentrations (Cmax) and extent of absorption (AUC) (see Table 1 below). Another study established that the 160 mg tablet is bioequivalent to 2 x 80 mg tablets as well as to 4 x 40 mg for both peak plasma concentrations (Cmax) and extent of absorption (AUC) (see Table 2 below). Given the short half-life of elimination of oxycodone from OxyContin ® , steady-state plasma concentrations of oxycodone are achieved within 24-36 hours of initiation of dosing with OxyContin Tablets.

In a study comparing 10 mg of OxyContin every 12 hours to 5 mg of immediate-release oxycodone every 6 hours, the two treatments were found to be equivalent for AUC and Cmax, and similar for Cmin (trough) concentrations. There was less fluctuation in plasma concentrations for the OxyContin Tablets than for the immediate-release formulation.

Hours From Dosing 0 1 2 3 4 5 6 7 89101112

Oxycodone

Concentration

(ng/ mL), Log Scale

1 10 100

XX X X X X X X X X XXX X X X X

X X X X

10 mg 20 mg 40 mg 160 mg Single Dose 10 mg q12h Steady-State X 80 mg

Plasma Oxycodone By Time