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PubMed1996

The pharmacokinetics of oxycodone in uremic patients undergoing renal transplantation.

STUDY OBJECTIVE: To determine the pharmacokinetics of oxycodone and the excretion of oxycodone and its metabolites noroxycodone and oxymorphone in uremic patients undergoing renal transplantation. DESIGN: Open study of the pharmacokinetics and excretion of oxycodone. SETTING: IV Department of Surgery, Helsinki University Central Hospital. PATIENTS: 10 uremic patients undergoing renal transplantation and 10 ASA status I patients undergoing general surgery. INTERVENTIONS: Intravenous (IV) oxycodone chloride 0.07 mg/kg was administered 30 minutes before induction of standardized anesthesia. Sampling of blood and urine was conducted for 24 hours. MEASUREMENTS AND MAIN RESULTS: The concentrations of oxycodone and noroxycodone in plasma and the 24 hour urine recoveries of the conjugated and unconjugated forms of oxycodone, noroxycodone, and oxymorphone were measured. Mean elimination half-life was prolonged in uremic patients due to increased volume of distribution and reduced clearance. Interindividual variation was very great. Plasma concentrations of noroxycodone were higher in uremic patients. Significantly smaller quantities of free oxycodone and noroxycodone and both free and conjugated oxymorphone were excreted in the urine in the uremic than in the control patients. CONCLUSIONS: Elimination of oxycodone is impaired in end-stage renal failure.

Adult↗

PubMed2006

Characterization of the antinociceptive effects of oxycodone in diabetic mice.

We investigated the antinociceptive efficacy of systemic and centrally injected oxycodone on thermal hyperalgesia in streptozotocin-induced diabetic mice. The antinociceptive response was assessed by recording the latency in the tail-flick test using the radiant heat from a 50-W projection bulb on the tail. The tail-flick latency in diabetic mice was significantly shorter than that in non-diabetic mice. Oral (p.o.) and i.t., but not i.c.v., administration of oxycodone prolonged the tail-flick latency in diabetic mice to a level that was considerably longer than the baseline latency in non-diabetic mice. However, morphine did not significantly inhibit the tail-flick response in diabetic mice. The antinociceptive effect of either p.o. or i.t. oxycodone in non-diabetic mice, but not in diabetic mice, was antagonized by pretreatment with a selective mu-opioid receptor antagonist, beta-funaltrexamine. In non-diabetic mice, pretreatment with a selective kappa-opioid receptor antagonist, nor-binaltorphimine, had no effect on the peak antinociceptive effect of either p.o. or i.t. oxycodone at 30 min after administration, however, it slightly but significantly reduced oxycodone-induced antinociception at 60 and 90 min after administration. On the other hand, pretreatment with nor-binaltorphimine practically abolished the antinociceptive effects of both p.o.- and i.t.-administered oxycodone in diabetic mice. Naltrindole, a selective delta-opioid receptor antagonist, had no effects on the antinociceptive effect of oxycodone in either non-diabetic or diabetic mice. These results suggest that the antinociceptive effects of oxycodone may be mediated by spinal kappa-opioid receptors in diabetic mice, whereas it may interact primarily with supraspinal and spinal mu-opioid receptors in non-diabetic mice.

Analgesics, Opioid↗

PubMed1999

Can a controlled-release oral dose form of oxycodone be used as readily as an immediate-release form for the purpose of titrating to stable pain control?

Two separate trials compared controlled-release (CR) oral oxycodone (administered every 12 hours) with immediate-release (IR) oxycodone (4 times a day) to determine whether patients with chronic pain could be titrated to stable pain control as readily with the CR as with the IR formulation. In one study, 48 patients with cancer pain were randomized to open-label titration with either CR or IR oxycodone (maximum dose, 400 mg/day) for a period of up to 21 days. In a study of similar design, 57 patients with low back pain were titrated with either CR or IR oxycodone (maximum dose, 80 mg/day) for a period of up to 10 days. The majority of patients in both studies were converted to oxycodone from other opioid analgesics. Results of both studies showed no difference between CR and IR oxycodone with respect to both the percentage of patients achieving stable pain control, the time to achieve stable pain control, and the degree of pain control achieved. Among cancer patients, 85% achieved stable analgesia, 92% with the CR formulation and 79% with the IR formulation. Among noncancer patients, 91% achieved stable pain control, 87% with the CR formulation and 96% with the IR formulation. The most commonly reported adverse effects in both studies were similar for the two formulations and were those anticipated with opioids: nausea, vomiting, constipation, somnolence, dizziness, and pruritus. Nausea and vomiting were the most frequently cited reasons for treatment discontinuations. These studies suggest that dose titration can be accomplished as readily with oral CR oxycodone as with IR oxycodone in patients with chronic, moderate to severe pain.

Adult↗

PubMed1997

Comparison of epidural morphine and oxycodone for pain after abdominal surgery.

STUDY OBJECTIVE: To compare the efficacy and side effects of epidural morphine and oxycodone for pain following major abdominal surgery. DESIGN: Randomized, double-blind study. SETTING: 4th Department of Surgery, Helsinki University Central Hospital. PATIENTS: 44 adult ASA physical status I, II, and III patients scheduled for elective major abdominal surgery. INTERVENTIONS: Thirty-three patients were allocated randomly to one of two epidural groups and 11 patients received oxycodone intravenously (IV). The two epidural groups received either morphine (bolus 0.015 mg/kg followed by an infusion 0.003 mg/kg/hr) or oxycodone (bolus 0.15 mg/kg followed by an infusion 0.03 mg/kg/hr) before induction of standardized anesthesia and for 24 hours thereafter. A third group of patients was given the same dose of IV oxycodone as in the epidural group, serving as an open control group for epidural oxycodone. MEASUREMENTS AND MAIN RESULTS: Blood samples were drawn for plasma opioid concentrations. Postoperatively, pain (at rest and during coughing), nausea, pruritus, sedation, respiratory rate, and hemodynamics were recorded until the end of the infusions. The epidural dose ratio between morphine and oxycodone was 1:8.4 to 9.8 to provide similar analgesia. Side effects occurred similarly in the three groups. Mild respiratory depression was seen in all groups, especially in the IV oxycodone group. In all groups, hemodynamic variables remained within normal limits. CONCLUSIONS: In the dosages reported, oxycodone can be used epidurally for acute post-operative pain. The analgesic effect was as good as that of epidural morphine.

Abdomen↗

PubMed1999

Comparison of the analgesic effects of intrabursal oxycodone and bupivacaine after acromioplasty.

STUDY OBJECTIVES: To compare the peripheral analgesic effect of oxycodone, an opioid agonist, to the effect of bupivacaine infiltration and parenteral oxycodone administration in conjunction with shoulder surgery. DESIGN: Prospective, randomized, double-blind study. SETTING: University teaching hospital. PATIENTS: 42 ASA physical status I and II patients scheduled for shoulder surgery with general anesthesia. INTERVENTIONS: Patients were randomized to three study groups: at the end of the surgery patients received either 10 ml of 0.5% bupivacaine (group BIB) or 5 mg of oxycodone in 10 ml of saline (group OIB) in the subacromial bursa; or 5 mg of oxycodone intramuscularly (group OIM). Postoperative analgesia was provided by patient-controlled analgesia (PCA). MEASUREMENTS AND MAIN RESULTS: The fentanyl requirements were recorded for the 24-hour postoperative period and the total perioperative period. Postoperative pain was assessed by visual analog scale for pain (VASP). Plasma oxycodone concentrations were measured in groups OIB and OIM. The total perioperative fentanyl consumption was significantly lower in groups BIB (0.97 +/- 0.09 mg) and OIB (1.23 +/- 0.12 mg) than in group OIM (1.61 +/- 0.12 mg) (p = 0.01 and 0.048, respectively). Groups BIB and OIB were similar (p = 0.34). The absorption of oxycodone was significantly lower after subacromial than after intramuscular administration. CONCLUSION: Intrabursal oxycodone and intrabursal bupivacaine reduced perioperative analgesic requirements similarly. Intrabursal oxycodone may offer an effective, simple, and safe method for postoperative analgesia after shoulder surgery.

Acromion↗

PubMed2000

Morphine or oxycodone in cancer pain?

Oxycodone is an opioid analgesic that closely resembles morphine. Oxymorphone, the active metabolite of oxycodone, is formed in a reaction catalyzed by CYP2D6, which is under polymorphic genetic control. The role of oxymorphone in the analgesic effect of oxycodone is not yet clear. In this study, controlled-release (CR) oxycodone and morphine were examined in cancer pain. CR oxycodone and morphine were administered to 45 adult patients with stable pain for 3-6 days after open-label titration in a randomized, double-blind, cross-over trial. Twenty patients were evaluable. Both opioids provided adequate analgesia. The variation in plasma morphine concentrations was higher than that of oxycodone, consistent with the lower bioavailability of morphine. Liver dysfunction affected selectively either oxycodone or morphine metabolism. Three patients with markedly aberrant plasma opioid concentrations are presented. Significant individual variation in morphine and oxycodone metabolism may account for abnormal responses during treatment of chronic cancer pain.

Administration, Oral↗

PubMed2004

Epidural oxycodone or morphine following gynaecological surgery.

BACKGROUND: The analgesic action of oxycodone is of rapid onset, in contrast to morphine, and is mediated by kappa-opioid receptors of the spinal cord. We compared analgesia and side-effects of epidural oxycodone with those of morphine after gynaecological surgery. METHODS: We studied prospectively in 75 women in a double-blind, randomized manner: epidural morphine 6 mg day(-1) (n=25), epidural oxycodone 6 mg day(-1) (n=25) and epidural oxycodone 12 mg day(-1) (n=25). All patients underwent gynaecological surgery under general (isoflurane and nitrous oxide) and epidural anaesthesia. Visual analogue scale (VAS) pain scores at rest and on coughing, verbal descriptive scale (VDS) satisfaction scores, sedation scores, pruritus scores and nausea/vomiting scores were recorded for 3 days after surgery. RESULTS: VAS pain scores at rest in patients who received oxycodone 6 mg day(-1) were higher than in patients who received morphine 6 mg day(-1) at 6 h and on the first postoperative day and were significantly higher than in patients who received oxycodone 12 mg day(-1) on the first postoperative day. Scores for nausea, vomiting and pruritus in patients who received oxycodone 6 mg day(-1) and 12 mg day(-1) were lower than those in patients who received morphine. No significant differences were seen in VAS at cough and VDS satisfaction scores between the three groups. CONCLUSION: Epidural oxycodone was as effective as morphine at the doses investigated, with fewer side-effects.

Adult↗

PubMed2003

Tentative identification of novel oxycodone metabolites in human urine.

Oxycodone is a semisynthetic codeine derivative that has been used both as an analgesic and antitussive. In the mid 1990s, OxyContin was introduced as a slow-release formulation of oxycodone for use in patients with moderate to severe chronic pain from such ailments as arthritis, vertebral disc disease, and cancer. Doctors wrote 6.9 million prescriptions for OxyContin from May 2000 through May 2001. Thus, it is no surprise that hospitals and medical examiners' offices across the country have seen an increasing number of admissions and deaths resulting from oxycodone abuse and overdose. The laboratory identifies oxycodone as part of its routine abused and therapeutic drug-testing procedures. Routine gas chromatographic analysis of bile or urine in many of these cases revealed unidentified peaks in the region of oxycodone that appeared to be oxycodone metabolites. In humans, the only documented metabolites of oxycodone are oxymorphone and N-desmethyloxycodone (noroxycodone). This study attempts to characterize these compounds as "presumptive" metabolites based on circumstantial evidence from known metabolic pathways of oxycodone in other species, as well as of other opiates and narcotic analgesics.

Analgesics, Opioid↗

PubMed1995

Pharmacokinetics and pharmacodynamics of oxycodone when given intravenously and rectally to adult patients with cancer pain.

The single-dose pharmacokinetics and pharmacodynamics of oxycodone administered by the intravenous and rectal routes were determined in 12 adult cancer patients with moderate to severe cancer pain (visual analog scale [VAS] score, approximately 5). Oxycodone was administered by the intravenous and rectal routes with open drug administration and a cross-over design. After single-dose intravenous administration (7.9 +/- 1.5 mg, mean +/- SD), the mean (+/- SD) terminal half-life was 3.4 h (+/- 1.1), the mean (+/- SD) plasma clearance was 45.4 L/h (+/- 10.1), and the mean (+/- SD) volume of distribution in the terminal phase was 3.0 L/kg (+/- 1.1). After rectal oxycodone (30 mg), the mean (+/- SD) absorption lag time was 0.52 h (+/- 0.29) and the mean (+/- SD) absolute bioavailability was 61.6% (+/- 30.2%). Intravenous oxycodone was associated with a rapid onset of pain relief (5-8 min) in contrast to the 0.5- to 1.0-h delay observed after rectal administration. However, rectal oxycodone provided analgesia of much longer duration (approximately 8-12 h) than did intravenous oxycodone (approximately 4 h). There were no significant differences (P > 0.05) in the incidence and severity of side effects between intravenous and rectal oxycodone. The marked interindividual variation observed in the pharmacokinetics and pharmacodynamics of oxycodone in this study emphasizes the need for individualized dosing regimens.

Administration, Rectal↗

PubMedDate not supplied

Sustained-release oxycodone dosing survey of chronic pain patients.

OBJECTIVE: To determine the dosing of sustained-release oxycodone that is typically prescribed to achieve pain relief in a mixed group of chronic pain patients. METHODS: One hundred twenty-eight chronic pain patients prescribed stable doses of sustained-release oxycodone for at least 6 months were identified through chart review. Total daily dosing for both long- and short-acting opioids were recorded for each patient. RESULTS: The prescribed frequency of dosing sustained-release oxycodone determined through clinical practice was twice daily for 33% of patients, with 67% requiring greater than twice daily dosing. Ninety-three percent of those using greater than twice daily dosing were prescribed sustained-release oxycodone 3 times daily. The median dose of sustained-release oxycodone was 80 mg for patients prescribed twice daily dosing, 60 mg when prescribed 3 times daily, and 120 mg when 4 times daily. Regularly scheduled, daily supplemental short-acting opioids were used by 47% of patients prescribed twice daily sustained-release oxycodone and 21% prescribed greater than twice daily dosing. The median total oxycodone-equivalent daily dosage (short- + long-acting opioids) was 80 mg for patients treated with either twice daily or greater than twice daily dosing. CONCLUSION: In a mixed group of chronic pain patients referred to a university pain management clinic, sustained-release oxycodone was prescribed more often than twice daily (usually every 8 hours) in 67% of patients. Patients maintained on every-12-hour dosing were twice as likely to use regularly scheduled, daily, short-acting opioids to achieve pain relief.

Adult↗

PubMed1992

Comparative oxycodone pharmacokinetics in humans after intravenous, oral, and rectal administration.

The pharmacokinetics of oxycodone have been determined after single-dose administration by the intravenous (4.6-7.3 mg), oral (tablets, 9.1 mg and syrup, 9.1 mg), and rectal (30 mg) routes, in 48 patients undergoing minor surgery. There were no significant differences in the mean elimination half-lives between the intravenous (5.45 +/- 1.43 h), oral tablets (5.65 +/- 1.13 h), oral syrup (4.80 +/- 1.13 h), and rectal suppository (5.40 +/- 1.19 h) formulations of oxycodone. After intravenous administration, the mean plasma clearance of oxycodone was 25.5 +/- 10.1 L/h and the mean volume of distribution at steady state was 2.5 +/- 0.8 L/kg. The mean normalized area under the curve (AUC/D) obtained after intravenous dosing (48.2 +/- 30.2 micrograms.h/L/mg) was more than twice the AUC/D values obtained after the administration of oxycodone tablets (19.8 +/- 3.5 micrograms.h/L/mg), oxycodone syrup (17.5 +/- 5.3 micrograms.h/L/mg), and rectal suppository (20.3 +/- 5.1 micrograms.h/L/mg), indicating that the amount of oxycodone reaching the systemic circulation after the extravascular routes of administration was < 50% of that obtained after intravenous dosing. The mean absorption lag times after oxycodone tablets (0.52 +/- 0.33 h), oxycodone syrup (0.48 +/- 0.40 h), and rectal suppository (0.76 +/- 0.47 h) were consistent with the onset of pharmacological effects reported by the patients.

Administration, Oral↗

PubMed1979

Comparison of the analgesic dose-effect relationships of nefopam and oxycodone in postoperative pain.

The analgesic dose-effect relationship of nefopam was compared in a double-blind randomised trial with that of oxycodone in immediate postoperative pain. Nefopam 15 mg or oxycodone 4 mg was given every 10 min i.v. (maximum six times) to patients in pain after upper abdominal surgery until their wound pain (scored 0-3) disappeared. The mean pain intensity (PI), initially 2.2 in both groups, descreased by approximately the same extent for up to two doses in both groups (to 1.5 after nefopam 30 mg and to 1.1 after oxycodone 8 mg). Thereafter PI was significantly less in the oxycodone group and diminished almost linearily to 0.1 after the sixth dose (24 mg). In the nefopam group, the PI score fell to 1.1 after the fourth dose (60 mg). This seemed to be the "ceiling" effect since additional doses up to 90 mg did not result in greater pain relief. In the oxycodone group, only two patients (12%) needed maximal dosage (6 x 4 mg), one of them requiring 32 mg of oxycodone. In the nefopam group, 12 patients (75%) needed further pain relief after the maximal dosage (6 x 15 mg). In these patients, oxycodone (maximally 16 mg) gave satisfactory analgesia. Drowsiness and a decrease in the respiratory rate were the principal side-effects of oxycodone, whereas tachycardia, restlessness, sweating and nausea were more frequent after nefopam.

Adult↗

PubMed2005

Marked variation in oxycodone pharmacokinetics in infants.

BACKGROUND: The pharmacokinetics of oxycodone (13-hydroxy-7,8-dihydrocodeinone) has been studied in adults and in children who are older than 6 months but there is no information on the disposition of oxycodone in neonates and young infants. The aim of this study was to study the pharmacokinetics of oxycodone in infants varying in age from 0 to 6 months. METHODS: Twenty-two infants undergoing surgery were given postoperatively an intravenous bolus of 0.1 mg.kg(-1) of oxycodone hydrochloride. Ten of the patients were younger than 1 week (group 1), six from 1 week to 2 months (group 2) and six from 2 to 6 months (group 3). Plasma samples were collected for the analysis of oxycodone concentrations up to 24 h. Pharmacokinetics were characterized by noncompartmental methods. RESULTS: The median (range) values for the clearance (Cl) were 9.9 (2.3-17.2), 20.1 (3.7-40.4) and 15.4 (14.8-80.2) ml.min(-1).kg(-1) in the above three groups. The values for volume of distribution at steady-state were 3.3 (1.9-4.7), 5.6 (1.3-8.5) and 3.2 (1.8-6.0) l.kg(-1) and for elimination half-life (t(1/2)) 4.4 (2.4-14.1), 3.6 (1.6-11.6) and 2.0 (0.8-3.9) h, respectively. Both Cl (r = 0.46) and half-life (r = -0.46) were correlated to the age of the patient (P < 0.05). There were 13 patients who were on mechanical ventilation at the time of oxycodone administration. None of the spontaneously breathing infants had hypoventilation which required assistance during the study. CONCLUSIONS: The values for Cl and t(1/2) varied greatly between the subjects. This variability was most pronounced in the two youngest groups. Routine dosing of oxycodone in young infants may be dangerous. The dose of oxycodone must be titrated individually.

Aging↗

PubMed1998

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). RESULTS: Pain intensity remained slight during the study, with mean oxycodone doses of 114 mg/d (range, 20 to 400 mg/d) for CR and 127 mg/d (range, 40 to 640 mg/d) for IR. Acceptability of therapy was fair to good with both treatments. While standard conversion ratios provided an acceptable dose for many patients, a protocol amendment that allowed initial titration and use of rescue medication reduced the discontinuation rate for lack of acceptable pain control (from 34% to 4% with CR and from 31% to 19% with IR before and after amendment, respectively) without increasing the discontinuation rate for adverse events (from 8% to 7% with CR and from 13% to 11% with IR). Fewer adverse events were reported with CR (109) than with IR (186) oxycodone (P=.006). CONCLUSION: CR oxycodone every 12 hours was as effective as IR oxycodone four times daily in managing moderate to severe cancer-related pain and was associated with fewer reports of adverse events.

Analgesics, Opioid↗

PubMed2003

Controlled-release oxycodone for pain in diabetic neuropathy: a randomized controlled trial.

BACKGROUND AND OBJECTIVE: Opioid treatment has played a limited role in the management of diabetic neuropathy, in part because of concerns about the responsiveness of neuropathic pain to opioid treatment. This controlled study evaluated the efficacy and safety of controlled-release (CR) oxycodone in subjects with moderate to severe pain due to diabetic neuropathy. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study included 159 subjects with moderate to severe pain due to diabetic neuropathy. Treatment began with either one 10-mg tablet of CR oxycodone (n = 82) or identical placebo (n = 77) every 12 hours. Doses could be increased every 3 days to a maximum of 6 tablets (60 mg CR oxycodone) every 12 hours. Treatment lasted up to 6 weeks. The primary efficacy variable was overall average daily pain intensity during study days 28 to 42. RESULTS: At an average (SD) dose of 37 (21) mg per day (range 10 to 99 mg/d), CR oxycodone provided more analgesia than placebo (p= 0.002) in the intent-to-treat cohort. From days 28 to 42, overall average daily pain intensity (least squares mean +/-SE), rated in subject diaries on a numeric scale of 0 (no pain) to 10 (pain as bad as you can imagine), was 4.1 +/- 0.3 in subjects given CR oxycodone and 5.3 +/- 0.3 in placebo-treated subjects. Overall, 80 (96%) of 82 subjects given CR oxycodone and 52 (68%) of 77 subjects who received placebo reported adverse events. The most common adverse events in the CR oxycodone group were opioid related. CONCLUSIONS: In this 6-week trial, CR oxycodone was effective for the treatment of moderate to severe pain due to diabetic neuropathy. Adverse events were typical of opioid-related side effects.

Aged↗

PubMed2004

The pharmacokinetics of oxycodone.

Oxycodone is among the most commonly used opioid analgesics for the relief of moderate-to-severe pain and is pharmacodynamically comparable to morphine. Oxycodone is available in the United States in oral dosage forms and controlled-release tablets. Studies have demonstrated marked interindividual variation in the pharmacokinetics of oxycodone. The pharmacokinetics of oral oxycodone differs from oral morphine in that it has a higher bioavailability, a slightly longer half-life, and is hepatically metabolized by cytochrome P450 rather than undergoing glucuronidation. Understanding oxycodone pharmacokinetics favors safe and effective use of this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and May 2004 relevant to the pharmacokinetics of oxycodone. These publications were reviewed and the literature summarized regarding unique and clinically important elements of oxycodone disposition including its absorption profile (immediate release, controlled release, rectal administration, and intranasal administration), distribution, and its metabolism/excretion. Special populations, including children and those with liver/renal failure, have a unique oxycodone pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.

Administration, Oral↗

PubMed1998

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. Patients received CR oxycodone tablets every 12 hr in a manner that reflected typical clinical practice. Supplemental immediate-release (IR) oxycodone was available PRN for breakthrough pain. Patients recorded medication use, adverse events, and evaluations of pain intensity and acceptability of therapy in a daily diary. Forty-four patients (51%) completed all 12 weeks of study; 43 patients (49%) discontinued participation. At baseline and throughout the study period, the overall mean pain-intensity score was slight to moderate. A comparison of initial and final doses showed a significant but modest increase in total daily CR oxycodone dose. An increase or decrease in titration of the oxycodone dose occurred for 66 patients (84%) at least once during the 12-week study period, primarily for increased pain. Forty-four patients (56%) did not undergo dose titration when the latter was indicated. Half of the patients used IR oxycodone rescue almost daily; the mean number of rescue doses per day was 1.5. Despite stable pain control and an increasing total daily CR oxycodone dose, the percentage of patients reporting common opioid-related adverse events decreased over the course of the study. CR oxycodone tablets administered every 12 hr were successfully used to manage cancer pain over a 12-week period. Importantly, side effects diminished over time without a concomitant change in efficacy.

Administration, Oral↗

PubMed2003

Postmortem oxycodone and hydrocodone blood concentrations.

There is limited data on postmortem oxycodone concentrations, consisting of three published reports with a total of 11 cases, many of which were polypharmacy cases. This report presents the results of a review of autopsy and coroner's reports from 10 counties for the years 2000 and 2001 to locate cases with oxycodone or hydrocodone exposure as a leading cause of death. Eighty-eight cases were located. Twenty-four deaths were attributed to oxycodone alone. Mean and median postmortem oxycodone blood concentrations were 1.23 mg/L and 0.43 mg/L, respectively. The range was 0.12 to 8.0 mg/L, with 13 cases (54%) < or = 0.5 mg/L. Seventeen deaths were attributed to hydrocodone alone. Mean and median postmortem hydrocodone blood concentrations were 0.53 mg/L and 0.40 mg/L, respectively. The range was 0.12 to 1.6 mg/L, with 11 cases (65%) < or = 0.5 mg/L. There were seven cases where the cause of death was attributed to the effects of a combination of hydrocodone and oxycodone. Mean oxycodone and hydrocodone blood concentrations were 0.34 mg/L and 0.14 mg/L, respectively. Forty cases involved polysubstance overdoses with significant involvement of other drugs and ethanol. Mean oxycodone and hydrocodone blood concentrations were 0.18 mg/L and 0.29 mg/L, respectively. The list of other substances involved was extensive but included ethanol, amitriptyline, methadone, codeine, propoxyphene, and acetaminophen. The findings of this study report oxycodone values associated with a fatality at blood concentrations lower than previously reported. This may represent enhanced information because of the larger sample group. Hydrocodone values associated with a fatality were similar to previously published values.

Adult↗