Controlled-release oxycodone compared with controlled-release morphine in the treatment of cancer pain: a randomized, double-blind, parallel-group study.

Controlled-release oral formulations of oxycodone and morphine are both suitable analgesics for moderate to severe pain. They were compared in cancer-pain patients randomized to double-blind treatment with controlled-release oxycodone (n = 48) or controlled-release morphine (n = 52) every 12 h for up to 12 days. Stable analgesia was achieved by 83% of controlled-release oxycodone and 81% of controlled-release morphine patients in 2 days (median).

Oral morphine and respiratory function amongst hospice inpatients with advanced cancer.

Background: Respiratory depression is the opioid adverse effect feared most by physicians. This may hinder adequate dosing in cancer pain. The study was conducted to examine the respiratory function of patients with advanced cancer receiving significant doses (>100 mg/24 h) of oral morphine.

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 =.

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.

Long-term administration of controlled-release oxycodone tablets for the treatment of cancer pain.

We conducted a study of the safety of controlled-release (CR) oxycodone tablets (OxyContin Tablets) administered chronically to patients with cancer-related pain in a usual clinical setting. These patients had participated in 1 of 2 double-blind, active-control studies. Our study was an open, 3-month treatment study that included 87 patients.

The use of controlled-release oxycodone for the treatment of chronic cancer pain: a randomized, double-blind study.

To compare the effectiveness and safety of controlled-release (CR) oxycodone tablets with immediate-release (IR) oxycodone in patients with chronic cancer pain, a multicenter, randomized, double-blind, parallel-group study was performed in 111 patients with cancer pain. Patients were treated with 6 to 12 tablets or capsules of fixed-combination opioid/nonopioid analgesics per day at study entry. Patients received 30 mg of CR oxycodone tablets every 12 hr or 15 mg of IR oxycodone four times daily for 5 days.

Comparison of controlled-release and immediate-release oxycodone tablets in patients with cancer pain.

Purpose: This study compared the clinical efficacy of oxycodone hydrochloride controlled-release (CR) tablets administered every 12 hours with immediate-release (IR) oxycodone tablets administered four times daily in patients with cancer-related pain.

Patients And Methods: Cancer patients who required therapy for moderate to severe pain were randomized to CR oxycodone every 12 hours (n=81) or IR oxycodone four times daily (n=83) for 5 days in a multicenter, double-blind study. Pain intensity was assessed four times daily (categorical scale of none, slight, moderate, and severe); acceptability of therapy was assessed twice daily (categorical scale of very poor, poor, fair, good, and excellent).

The effect of food intake on the pharmacokinetics of sustained-release morphine sulfate capsules.

The effect of food intake on the pharmacokinetics of sustained-release (SR) morphine sulfate capsules was assessed in 24 healthy male volunteers. Subjects were randomized to receive a single, 20-mg SR morphine sulfate capsule while fasting and immediately after consumption of a standard high-fat meal. Plasma samples were masked for pharmacokinetic analysis.

Pharmacokinetics and pharmacodynamics of controlled-release opioids.

While pharmacokinetic/pharmacodynamic relationships for opioids have not been consistently demonstrable or sufficiently predictive, there remain compelling reasons to pursue such relationships. Among the reasons for pursuing pharmacokinetic/ pharmacodynamic relationships is the prospect of predicting the time-action characteristics of new therapeutics on the basis of early studies in normals using pharmacodynamic surrogates for analgesia. The realization of such a model could improve the efficiency of development of analgesics.

Characterization and validation of a pharmacokinetic model for controlled-release oxycodone.

1. Oxycodone is a strong opioid agonist that is currently available in immediate-release (IR) formulations for the treatment of moderate to severe pain. Recently, controlled-release (CR) oxycodone tablets were developed to provide the benefits of twice-a-day dosing to patients treated with oxycodone.

Analgesic efficacy of controlled-release oxycodone in postoperative pain.

The efficacy and safety of graded doses (10, 20, and 30 mg) of controlled-release (CR) oxycodone was compared with that of immediate-release (IR) oxycodone (15 mg), immediate-release oxycodone 10 mg in combination with acetaminophen 650 mg (APAP), and placebo in a single-dose, double-blind, randomized, parallel-group study. The participants, 182 inpatients experiencing moderate to severe pain after abdominal or gynecologic surgery, provided hourly ratings of pain intensity and relief for 12 hours after administration. All active treatments were significantly superior to placebo for many hourly measurements and for the sum of pain intensity differences (SPID) and total pain relief (TOTPAR).

Differential effects of food on the bioavailability of controlled-release oxycodone tablets and immediate-release oxycodone solution.

The effects of a high-fat meal on the bioavailability of oxycodone hydrochloride, administered as a recently developed 40 mg controlled-release (CR) tablet or a 20 mg immediate-release (IR) solution, were evaluated in a randomized crossover study in 22 normal male and female subjects. Serial blood samples were collected for 36 h after dosing and analyzed for oxycodone by a validated method using gas chromatography/mass spectrometry. There was no significant food effect with CR oxycodone as judged by 90% confidence interval (CI) analysis of AUC0-infinity and Cmax values under fed and fasted conditions.

Steady-state bioavailability of controlled-release oxycodone in normal subjects.

The steady-state bioavailability of a controlled-release (CR) oxycodone tablet was compared with that of an immediate-release (IR) oxycodone solution in a randomized, analytically masked, multiple-dose, crossover study in 24 normal subjects. Each subject received either one 10-mg CR oxycodone tablet every 12 hours for 4 days or 5 mL of a 1-mg/1 mL IR oxycodone solution every 6 hours for 4 days. Steady state was achieved after approximately 1 day of dosing.

Pharmacokinetic-pharmacodynamic relationships of controlled-release oxycodone.

Plasma concentrations of oxycodone, oxymorphone, and noroxycodone were determined after administration of 20 mg oral controlled-release oxycodone tablets to four subject groups: young (aged 21 to 45 years) men, elderly (aged 65 to 79 years) men, young women, and elderly women. Area under the oxycodone and noroxycodone concentration-time curve (AUC) values were comparable among the four groups. Compared with oxycodone, the oxymorphone AUC values were small, with significant differences between subject groups.

Relative bioavailability of controlled-release oral morphine sulfate during naltrexone blockade.

The effect of naltrexone hydrochloride on the bioavailability of 60 mg controlled-release oral morphine sulfate in normal volunteers was determined using a randomized, 2-way crossover, analytically blinded study design. Although naltrexone did not qualitatively alter the concentration-time curve for controlled-release morphine, the area under the plasma morphine concentration-time curve from 0-24 h (AUC0-24) was significantly greater (p < 0.01) for morphine given with naltrexone (265 ng x h/ml) than for morphine given alone (215 ng x h/ml).

A bioequivalence study of oral controlled-release morphine using naltrexone blockade.

Twenty-three normal volunteers who received morphine sulphate (MS Contin) with naltrexone completed this randomized, analytically blinded, two-way crossover comparison of the bioavailability of one 200-mg oral controlled-release morphine sulfate tablet with two 100-mg MSC tablets. Morphine effects were blocked by three 100-mg doses of naltrexone. The first dose of naltrexone was given 24 hours before MSC dosing, followed by a second dose at the time of MSC dosing and a third dose 24 hours after MSC administration.

Analgesic efficacy and safety of two oral controlled-release morphine preparations in orthopedic postoperative pain.

This single-dose, double-blind, randomized, parallel-group study compared the analgesic efficacy and safety of MS Contin (MSC) and Oramorph SR (OSR), two controlled-release preparations of oral morphine sulfate, in patients following orthopedic surgery. One hundred patients received MSC 30 mg, MSC 60 mg, or OSR 60 mg (two 30-mg tablets) when postoperative pain became moderate or severe. Patients self-rated pain intensity and relief on categorical (CAT) and visual analogue scales (VAS) hourly for up to 12 hours.

Analgesic efficacy and potency of two oral controlled-release morphine preparations.

MS Contin tablets and Oramorph SR tablets are two forms of oral controlled-release morphine sulfate available for the alleviation of pain. Our objective was to compare their analgesic effects in a relative potency assay. In this study, 151 patients undergoing caesarean section or abdominal hysterectomy and reporting moderate or severe postoperative pain received a 30 or 90 mg dose of either drug in a balanced, randomized, double-blind, parallel-group, single-dose experimental design.

The bioavailability of morphine in controlled-release 30-mg tablets per rectum compared with immediate-release 30-mg rectal suppositories and controlled-release 30-mg oral tablets.

The bioavailability of controlled-release morphine 30-mg tablets (MSC) administered orally or rectally and immediate-release morphine (RMS) 30-mg suppositories per rectum, was compared in this 14-subject, randomized, single-dose, analytically blinded, crossover study. Rectal MSC plasma morphine area under the curve from 0-24 hours (AUC0-24) was 50.8% of RMS and was similar for MSC administered by either route (rectal MSC = 90% oral MSC).

Comparison of the pharmacokinetic profiles of two oral controlled-release morphine formulations in healthy young adults.

The pharmacokinetic profiles of two oral controlled-release morphine formulations, MS Contin tablets and Roxanol SR tablets, were compared to evaluate their bioequivalence. In a sequential, crossover study, 18 healthy young male volunteers received single 60-mg doses (two 30-mg tablets) of each formulation and provided 15 serial blood samples over 24 hours, which were assayed to determine their morphine concentrations by high-performance liquid chromatography. Analysis of variance revealed significant differences between the treatments for maximum plasma concentration (P less than 0.

Relationships between opioid disposition and their pharmacological effects--an overview.

The understanding of the metabolic disposition and pharmacokinetics of opioid analgesics and their relationship to therapeutic and adverse effects has been an area of considerable research activity in the past two decades and has provided the beginning of an applied science in this area. Given the experimental nature and complexity of pharmacokinetic/pharmacodynamic relationships and the state of the art in this area, the most meaningful therapeutic conclusions and extrapolations remain those based on the results of the most adequate and well-controlled therapeutic evaluations. In contrast, advances in analytical methodology and an understanding of the pharmacokinetics of opioid analgesics in specific patient populations (e.

Controlled-release morphine bioavailability (MS Contin tablets) in the presence and absence of food.

The bioavailability of a single, orally administered, 30-mg controlled-release morphine tablet (MS Contin Tablet; The Purdue Frederick Company, Norwalk, Conn.) was compared after fasting or a high fat meal in this single dose, randomized, crossover study involving 24 healthy male subjects. There was no significant (p greater than 0.

Cancer pain management with a controlled-release oral morphine preparation.

An open-label pilot study was conducted to assess the efficacy and acceptability of a controlled-release oral morphine formulation, MS Contin tablets, when administered "by the clock" two to three times daily as a substitute for opioids given on request to patients with pain caused by advanced cancer. Initially, four-hourly does of standard "immediate-release" oral morphine sulfate tablets were substituted for the patients' prior analgesic medication and titrated to individual needs. Forty of the 47 patients enrolled in the study were subsequently switched to an eight-hourly MS Contin regimen (three patients became too ill to continue the study, and four left the study during the immediate-release titration phase because of adverse reactions that may have been drug related).

Evaluation of a cancer pain model for the testing of long-acting analgesics. The effect of MS Contin in a double-blind, randomized crossover design.

A double-blind, double-dummy, crossover study compared oral controlled-release morphine sulfate (MS Contin tablets [MSC], Purdue Frederick, Norwalk, CT) every 12 hours, and immediate-release morphine sulfate (IRMS) tablets, every 4 hours, in 14 evaluable patients with chronic cancer pain. The test model described showed assay sensitivity for steady-state analgesia, requiring relatively few subjects to yield statistical significance in pharmacologic potency estimates. Initial doses were the calculated equivalents of about one third the previous opioid requirements or at least 30 mg MSC every 12 hours or 15 mg IRMS every 4 hours.