Relative variability in bioavailability of oral controlled-release formulations of oxycodone and morphine.

A retrospective analysis compared the coefficients of variation associated with the maximum plasma concentration (Cmax) and the extent of absorption (area under the curve [AUC] from 0 hour to the last observation) for oral, controlled-release tablet formulations of oxycodone (OxyContin) and morphine (MS Contin). Data from fasting, male subjects aged 18 to 45 years were taken from five controlled-release oxycodone (N = 82) and seven controlled-release morphine (N = 101) single-dose, bioequivalence studies. The coefficients of variation of Cmax and AUC were approximately 33% less for controlled-release oxycodone than for controlled-release morphine (P =.005). The variation from the minimum to maximum value was two to three times less for controlled-release oxycodone than for controlled-release morphine. Among healthy male subjects, the absorption of oxycodone from oral controlled-release oxycodone was significantly more consistent than the absorption of morphine from oral controlled-release morphine in terms of both maximum absorption and extent of absorption.

Efficacy and safety of controlled-release versus immediate-release oxycodone: randomized, double-blind evaluation in patients with chronic back pain.

OBJECTIVE: To compare the efficacy and safety of controlled-release oxycodone given every 12 hours with immediate-release oxycodone given four times daily in patients with persistent back pain. DESIGN: Randomized, double-blind, active-controlled, two-period crossover trial. PATIENTS: Fifty-seven adult outpatients with stable, chronic, moderate-to-severe low back pain despite analgesic therapy were enrolled; 47 were randomized; 11 discontinued for side effects, most commonly nausea and vomiting. INTERVENTIONS: Controlled-release oxycodone tablets given every 12 hours; immediate-release oxycodone tablets given four times daily; dose titration with controlled-release or immediate-release for up to 10 days; double-blind treatment for 4-7 days each. OUTCOME MEASURES: Patients' pain scores (0 = none, 1 = slight, 2 = moderate, 3 = severe). RESULTS: Pain intensity decreased from moderate to severe at baseline to slight at the end of titration with both oxycodone formulations. The daily oxycodone dose was 40 mg or less in 68% of patients. During double-blind treatment, mean pain intensity was maintained at 1.2 (0.1 SE) with controlled-release and at 1.1 (0.1 SE) with immediate-release oxycodone. The most common adverse events were constipation, nausea, pruritus, somnolence, and dizziness. CONCLUSIONS: Controlled-release oxycodone given every 12 hours was comparable with immediate-release oxycodone given four times daily in efficacy and safety, and it provides convenient, twice-daily, around-the-clock treatment for selected patients with persistent back pain that is inadequately controlled by nonopioids or as-needed opioid therapy.

A pharmacokinetic/pharmacodynamic study of controlled-release oxycodone.

A single-dose, analytically blinded, randomized, crossover study was conducted in 22 healthy male volunteers to compare the bioavailability of one 20 mg with two 10 mg controlled-release (CR) oxycodone tablets. In addition, pharmacodynamic effects were assessed using both objective and subjective measures for up to 48 hr after dosing. The two treatments were bioequivalent, with comparable rates (Cmax of one 20 mg tablet was 109% of two 10 mg tablets; 90% confidence limits: 98.4%-120%) and extents (AUC0-infinity: 107%; 100%-114%) of absorption. In addition, no significant differences between tablets were found for mean values of Tmax, T/12abs, or T/12elim. Correlations between plasma oxycodone concentrations and most pharmacodynamic measures were significant. The strongest correlations were observed for pupil size (r = -0.53) and subjects' assessment of drug effect (r = 0.53), with changes in plasma concentration accounting for more than 25% of the observed changes in these variables. This study demonstrated bioequivalence of two 10 mg and one 20 mg CR oxycodone tablet, with significant correlation between plasma oxycodone concentrations and pharmacodynamic effects in normal volunteers.

Quantitation of the third component of complement on stored red cells.

By means of an automated anti-C3c consumption technic, we quantitated the molecules of the third component of human complement (containing the C3c fragment) that accumulate on red cells (RBCs) during liquid whole-blood storage. Calibrated C-3 sensitized zymosan particles ( ZyC3 ) were used as standards for bound C3. Although the dose-response curves of anti-C3c neutralization by ZyC3 and stored RBCs were similar, mathematical analysis showed that the shapes of these two sigmoidal curves were significantly different. This indicated that the large C3 molecules bound to stored RBCs differed antigenically from those bound to ZyC3 . Despite this difference, the former could be quantitated adequately by the automated anti-C3c consumption technic. Red cell-bound large C3 molecules were measured following various periods of storage at 4 degrees C of whole blood samples (n=102). An average of 48 molecules were detected on RBCs stored for 21 days. Statistical analysis of these data indicated that during storage at 4 degrees C there was a continuous accumulation of C3 on RBCs, followed by cleavage of C3c fragments. The degree of agglutination of stored RBCs with anti-C3c was proportional to the number of cell-bound large C3 molecules.