Plasma Concentrations Of Oxycodone Research Articles

Analgesic Efficacy of Oxycodone in Postoperative Dressings after Surgical Treatment of Burn Wounds: A Randomised Controlled Trial

Introduction: This study aimed to assess the analgesic efficacy of oxycodone at doses of 10 mg and 20 mg in dressings after surgery of burn wounds. Material and Methods: Twenty adult patients who underwent surgical treatment of third-degree burn wounds under general anaesthesia were included. Burn wounds were treated with dressings, to which oxycodone was added at 20 mg in Group 1 and 10 mg in Group 2. After the surgery, plasma oxycodone and noroxycodone concentrations were assayed, and pain intensity was assessed with Numerical Rating Scale (NRS). Results: In Group 1, no patient reported pain; in Group 2, four patients reported pain. The pain intensity, according to NRS, was 1–8. Plasma concentration of oxycodone in the blood serum was in the range of 1.24–3.15 ng/mL and 1.09–1.28 ng/mL in Group 1 and Group 2, respectively. Noroxycodone was not detected in the plasma. Adverse effects were not observed in any of the treated patients. Conclusions: Oxycodone in dressings provides patients with adequate and safe analgesia.

Physiologically based pharmacokinetic modeling of ritonavir-oxycodone drug interactions and its implication for dosing strategy

The concomitant administration of ritonavir and oxycodone may significantly increase the plasma concentrations of oxycodone. This study was aimed to simulate DDI between ritonavir and oxycodone, a widely used opioid, and to formulate dosing protocols for oxycodone by using physiologically based pharmacokinetic (PBPK) modeling. We developed a ritonavir PBPK model incorporating induction and competitive and time-dependent inhibition of CYP3A4 and competitive inhibition of CYP2D6. The ritonavir model was evaluated with observed clinical pharmacokinetic data and validated for its CYP3A4 inhibition potency. We then used the model to simulate drug interactions between oxycodone and ritonavir under various dosing scenarios. The developed model captured the pharmacokinetic characteristics of ritonavir from clinical studies. The model also accurately predicts exposure changes of midazolam, triazolam, and oxycodone in the presence of ritonavir. According to model simulations, the steady-state maximum, minimum and average concentrations of oxycodone increased by up to 166% after co-administration with ritonavir, and the total exposure increased by approximately 120%. To achieve similar steady-state concentrations, halving the dose with an unchanged dosing interval or doubling the dosing interval with an unaltered single dose should be practical for oxycodone, whether formulated in uncoated or controlled-release tablets during long-term co-medication with ritonavir. The results revealed exposure-related risks of oxycodone-ritonavir interactions that have not been studied clinically and emphasized PBPK as a workable method to direct judicious dosage.

Enzalutamide Reduces Oxycodone Exposure in Men with Prostate Cancer.

Up to 90% of patients with castration-resistant prostate cancer (CRPC) will develop symptomatic bone metastases requiring pain medication, with opioids being the mainstay of therapy in treating moderate and severe pain. Enzalutamide is an androgen receptor antagonist for the treatment of CRPC and a strong inducer of cytochrome P450 (CYP)3A4. Hereby, enzalutamide potentially reduces the exposure of oxycodone, an opioid metabolized by CYP3A4 and CYP2D6. Our objective was to evaluate the potential drug-drug interaction of enzalutamide and oxycodone. A prospective, nonrandomized, open-label, two-arm parallel study was performed. All patients received a single dose of 15mg normal-release oxycodone. Patients in the enzalutamide arm (ENZ-arm) received enzalutamide 160mg once daily. Plasma concentrations of oxycodone and its metabolites were quantified using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Twenty-six patients (13 ENZ-arm; 13 control arm) were enrolled in the study. Enzalutamide decreased the mean AUC0-8h and Cmax of oxycodone with, respectively, 44.7% (p < 0.001) and 35.5% (p = 0.004) compared with the control arm. The AUC0-8h and Cmax of the active metabolite oxymorphone were 74.2% (p < 0.001) and 56.0% (p = 0.001) lower in the ENZ-arm compared with the control arm. In contrast, AUC0-8h and Cmax of the inactive metabolites noroxycodone and noroxymorphone were significantly increased by enzalutamide. Co-administration of enzalutamide significantly reduced exposure to oxycodone and its active metabolite oxymorphone in men with prostate cancer. This should be taken into account when prescribing enzalutamide combined with oxycodone.

Oxycodone for pain management in the latent phase of labour - A pragmatic trial.

Parenteral opioids are used for pain relief in labour but there are little data for oxycodone in this context. The aim of this study was to evaluate the efficacy, foetal exposure and safety of subcutaneous oxycodone in the latent phase of labour. This pragmatic trial included 76 parturients, who received subcutaneous oxycodone for pain relief in the latent phase of labour according to the hospital protocol: an initial dose 0.1mg/kg, and a second dose, 0.05mg/kg, could be administered four hours later. Pain intensity and pain relief were assessed using a numerical rating scale of 0-10. After delivery, blood samples from the maternal and umbilical veins were collected, and plasma concentrations of oxycodone and its main metabolites were quantified using UPLC-MS/MS. The Apgar scores and maternal and neonatal adverse effects were recorded. The foetal exposure at birth was low, the median oxycodone and oxymorphone umbilical vein plasma concentrations were 1.2ng/mL (range 0.21-7.8) and 0.14ng/mL (0-0.26), respectively. Pain scores decreased substantially, from a median pain score of 7/10 before oxycodone to median scores of 5/10 at 30minutes after administration, 5/10 at 60minutes and 6/10 at 120minutes. The median Apgar score was 9 (range 2-10) at 1minute and 9 (6-10) at 5minutes. Maternal adverse effects were mild, and there were no oxycodone-related neonatal adverse effects. Subcutaneous oxycodone provided effective analgesia during the latent phase of labour. Newborn exposure at birth was low, and oxycodone was well-tolerated.

Optimization of Individual Pharmacotherapy Based on Multiple Evaluations of Patient Data

To date, limited drug information is available for the individual optimization of pharmacotherapy. The author attempted multiple evaluations of patient data on factors related to the pharmacokinetics, drug efficacy, and adverse reactions observed in clinical settings. Through the clinical studies, drug information on the individual optimization of pharmacotherapy needed by health professionals including physicians and pharmacists was identified. Major findings were: 1) Cachectic cancer patients had high plasma concentrations of oxycodone via the reduction of CYP3A activity. The metabolic reduction in cachectic cancer patients was potentially related to the elevated serum level of interleukin-6. 2) Dopamine receptor D2 (DRD2) genetic mutations and being female led to poor antiemetic efficacy of the treatment of opioid-induced nausea in prochlorperazine-treated patients. The opioid receptor μ1 (OPRM1) wild genotype in addition to being female and having high plasma concentrations of prochlorperazine increased prolactin secretion during oxycodone treatment. 3) Rheumatoid arthritis patients with a genetic mutation of ATP-binding cassette subfamily B member 1 (ABCB1) had high plasma concentrations of tacrolimus and its 13-O-demethylate. The ABCB1 genetic mutation and associated high plasma concentration of tacrolimus decreased kidney function. 4) Chronic inflammation increased the plasma voriconazole concentration via its poor metabolism, whereas it did not alter the plasma itraconazole concentration. Although co-administration of prednisolone did not affect the plasma concentration of triazole antifungals, it weakly increased voriconazole metabolism. 5) In breastfeeding women, the median milk/plasma concentration ratio of amlodipine was 0.85. However, the observed relative infant dose of amlodipine in most patients was less than 10%.

Association Study between Genes Related to Pharmacokinetics andPharmacodynamics of Oxycodone and Response to Drug Treatment: AGenetic Cohort Study

Objective: Oxycodone is widely used in cancer patients with pain, but interindividual differences in both its analgesic efficacy and adverse effects are major clinical disadvantages to therapeutic use. To explore specific polymorphisms affecting drug plasma concentrations, analgesic efficacy, and adverse effects, we performed an association study between genetic polymorphisms affecting pharmacokinetics and pharmacodynamics of oxycodone and response to drug treatment in cancer patients with pain. Methods: Blood samples were collected from 50 patients 12 h after administration of oxycodone. Genetic polymorphisms related to the pharmacokinetics and pharmacodynamics of oxycodone [cytochrome P450 (CYP3A4*1G, CYP3A5*3, and CYP2D6*10), P-glycoprotein (ABCB1), and opioid receptor μ1 (OPRM1)] were genotyped by real-time polymerase chain reaction (PCR) and plasma concentrations of oxycodone and noroxycodone were determined by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Results: Carriers of specific polymorphisms (CYP3A4 *1G/*1G, CYP3A5 *1/*1, CYP2D6 100CC+CT, and ABCB1 2677TA+TT+AA) were associated with increased average total daily dose of oxycodone. CYP3A4 *1G/*1G and CYP3A5 *1/*1 were also associated with increased number of rescues and plasma concentration of oxycodone. Moreover, OPRM1 118AG+GG carriers were related to greater average total daily dose of oxycodone and increased number of rescues. Conclusion: These findings suggest that genetic polymorphisms of genes related to pharmacokinetics and pharmacodynamics of oxycodone have a potential impact on clinical responses to drug in cancer patients with pain.

A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Intranasal Human Abuse Potential Study of Oxycodone ARIR, a Novel, Immediate-Release, Abuse-Deterrent Formulation.

ObjectivePrescription opioid abuse continues to be a public health concern. Oxycodone ARIR is an immediate-release (IR) oxycodone tablet composed of multiple overlapping barriers that deter manipulation of the tablet for non-oral abuse.DesignThis randomized, double-blind, double-dummy, active- and placebo-controlled, four-way crossover, intranasal human abuse potential study assessed the pharmacodynamics and pharmacokinetics of crushed intranasal oxycodone ARIR compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR.Outcome MeasuresPharmacodynamic end points included mean maximum drug liking (Emax), as measured by subjects on a bipolar 100-mm visual analog scale (primary), and desire to take the drug again, overall drug liking, drug high, and good effects (secondary). Pharmacokinetic assessments included peak concentration and time to peak concentration.ResultsTwenty-nine subjects completed the treatment phase. Crushed intranasal oxycodone ARIR demonstrated a significant reduction of 46.9% and 23.4% in drug liking Emax compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR, respectively (P < 0.0001 for both). Significant reductions also were observed in desire to take the drug again, drug high, overall drug liking, and good effects when comparing crushed intranasal oxycodone ARIR with crushed intranasal IR oxycodone and intact oral oxycodone ARIR (P < 0.001 for all). Crushed intranasal oxycodone ARIR exhibited lower peak oxycodone plasma concentrations and slower time to peak concentration compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR. All treatments were well tolerated; adverse effects were typical of opioids or intranasal administration.ConclusionsThese data indicate that oxycodone ARIR has the potential to reduce abuse via the intranasal route.

A prospective, randomized, open label, controlled study investigating the efficiency and safety of 3 different methods of rectus sheath block analgesia following midline laparotomy.

Background:There is a controversy regarding the efficacy of rectus sheath block (RSB). The aim of the present study was to evaluate analgesic efficacy and safety of three different methods of RSB in postoperative pain management after midline laparotomy.Methods:A prospective, randomized, controlled, open-label clinical trial with 4 parallel groups was conducted in a tertiary care hospital in Finland. A total of 57 patients undergoing midline laparotomy were randomized to the control group (n = 12) or to 1 of the 3 active RSB analgesia groups: single-dose (n = 16), repeated-doses (n = 12), or continuous infusion (n = 17). Opioid consumption with iv-patient-controlled analgesia pump was recorded, and pain scores and patients’ satisfaction were surveyed on an 11-point numeric rating scale for the first 48 postoperative h. Plasma concentrations of oxycodone and levobupivacaine were analyzed. All adverse events during the hospital stay were recorded.Results:Oxycodone consumption was less during the first 12 h in the repeated-doses and in the continuous infusion groups (P = .07) and in numerical values up to 48 h in the repeated-doses group. Plasma oxycodone concentrations were similar in all 4 groups. Pain scores were lower in the repeated-doses group when coughing during the first 4 h (P = .048 vs. control group), and at rest on the first postoperative morning (P = .034 vs. the other 3 groups) and at 24 h (P = .006 vs. the single-dose group). All plasma concentrations of levobupivacaine were safe. The patients’ satisfaction was better in the repeated-doses group compared with the control group (P = .025). No serious or unexpected adverse events were reported.Conclusions:RSB analgesia with repeated-doses seems to have opioid sparing efficacy, and it may enhance pain relief and patients’ satisfaction after midline laparotomy.

Analgesic efficacy and safety of epidural oxycodone in patients undergoing total hip arthroplasty: a pilot study.

Background and objectivesOxycodone is poorly studied as an adjuvant to central blockades. The aim of this pilot study was to assess the efficacy and safety of oxycodone hydrochloride in epidural blockade among patients undergoing total hip arthroplasty (THA).Patients and methodsIn 11 patients (American Society of Anesthesiologists physical status classification system II/III, age range: 59–82 years), THA was conducted with an epidural blockade using 15 mL 0.25% bupivacaine (37.5 mg) with 5 mg oxycodone hydrochloride and sedation with propofol infusion at a dose of 3–5 mg/kg/h. After the surgery, patients received ketoprofen at a dose of 100 mg twice daily. In the first 24 hours postoperative period, pain was assessed by numerical rating scale at rest and on movement; adverse effects (AEs) were recorded; and plasma concentrations of oxycodone, noroxycodone, and bupivacaine were measured.ResultsThe administration of epidural oxycodone at a dose of 5 mg in patients undergoing THA provided analgesia for a mean time of 10.3±4.89 h. In one patient, mild pruritus was observed. Oxycodone did not evoke other AEs. Plasma concentrations of oxycodone while preserving analgesia were >2.9 ng/mL. Noroxycodone concentrations in plasma did not guarantee analgesic effect.ConclusionThe administration of epidural oxycodone at a dose of 5 mg prolongs the analgesia period to ~10 hours in patients after THA. Oxycodone may evoke pruritus. A 5 mg dose of oxycodone hydrochloride used in an epidural blockade seems to be a safe drug in patients after THA.

Analgesic Plasma Concentrations of Oxycodone After Surgery for Breast Cancer-Which Factors Matter?

We investigated factors affecting analgesic oxycodone concentrations after breast cancer surgery in 1,000 women. Preoperatively, we studied heat and cold pain sensitivities and anxiety scores. Postoperatively, rest and motion pain intensities were measured and intravenous oxycodone was administered until satisfactory analgesia. At this point, the mean oxycodone concentration (variation coefficient) was 33.3 ng/mL (66%) and it was 21.7 ng/mL (69%) when the patient requested oxycodone again. At both time points, the concentrations varied >100-fold between individuals. The analgesic oxycodone concentration was increased by 21.3% per motion pain intensity score on a 0-10 scale and by 22.3% if axillary clearance was performed instead of sentinel node biopsy (P < 0.001). Forty-seven women who were older and less anxious than others (P < 0.01) required no oxycodone. Anxiety, age, chronic pain, or preoperative pain sensitivity were not independently associated with the analgesic oxycodone concentration. CYP2D6 and CYP3A genotypes did not affect analgesic concentration or duration of analgesia.

Oral Human Abuse Potential of Oxycodone DETERx® (Xtampza® ER)

Oxycodone DETERx® (Collegium Pharmaceutical Inc, Canton, Massachusetts) is an extended‐release, microsphere‐in‐capsule, abuse‐deterrent formulation designed to retain its extended‐release properties after tampering (eg, chewing/crushing). This randomized, double‐blind, placebo‐controlled, triple‐dummy study evaluated the oral abuse potential of intact and chewed oxycodone DETERx capsules compared with crushed immediate‐release oxycodone. Subjects with a history of recreational opioid use who were nondependent/nontolerant to opioids were enrolled. Treatments included intact oxycodone DETERx (high‐fat, high‐calorie meal and fasted), chewed oxycodone DETERx (high‐fat, high‐calorie meal and fasted), crushed immediate‐release oxycodone (fasted), and placebo (high‐fat, high‐calorie meal). Plasma samples were collected to determine pharmacokinetic parameters. The primary endpoint was drug liking at the moment; other endpoints included drug effects questionnaire scores, Addiction Research Center Inventory/Morphine Benzedrine Group score, pupillometry measurements, and safety. Thirty‐eight subjects completed the study. Chewed and intact oxycodone DETERx were bioequivalent, unlike crushed immediate‐release oxycodone, which yielded higher peak oxycodone plasma concentrations compared with all methods of oxycodone DETERx administration. The mean maximum (peak) effect (Emax) for drug liking was significantly lower for chewed and intact oxycodone DETERx than for crushed immediate‐release oxycodone (P < .01). The time to Emax was significantly longer for chewed and intact oxycodone DETERx than for crushed immediate‐release oxycodone (P < .0001). Scores for feeling high and Addiction Research Center Inventory/Morphine Benzedrine Group scores demonstrated lower abuse potential for chewed and intact oxycodone DETERx compared with crushed immediate‐release oxycodone. Study treatments were well tolerated; no subjects experienced serious adverse events. These results demonstrate the lower oral abuse potential of chewed and intact oxycodone DETERx than crushed immediate‐release oxycodone.

Dialyzability of Oxycodone and Its Metabolites in Chronic Noncancer Pain Patients with End-Stage Renal Disease.

Opioids are the preferred analgesic drugs to treat severe chronic pain conditions among dialysis patients; however, knowledge about their dialyzability features is limited. Oxycodone is increasingly used for the treatment of chronic pain conditions as oral controlled release (CR) tablets; however, evidence about this drug and its metabolites' dialyzability is lacking. We assessed, during 4-hour dialysis sessions, the effect of standard hemodialysis (HD) and online hemodiafiltration (HDF) methods on the plasma concentration of oxycodone and its metabolites in n = 20 chronic pain patients with end-stage renal disease who were stably treated with oral CR oxycodone. Chromatographic techniques were used to evaluate the studied compounds' plasma concentrations at three different time points during dialysis. Mean plasma concentrations of oxycodone and noroxycodone in the sample showed an overall reduction trend over time, but it was less enhanced for noroxycodone. Mean reduction in oxycodone and noroxycodone arterial concentrations was significant and higher with HDF (54% and 27%, respectively) than with HD (22% and 17%, respectively). Analysis of the regression of these compounds' clearance on their increasing arterial concentration showed a more stable and linear clearance prediction with HDF (roughly 85 mL/min); with HD, for increasing arterial concentration, clearance of oxycodone decreased while noroxycodone clearance increased. While no oxymorphone or noroxymorphone metabolites were detected, limited dialyzability of oxycodone and noroxycodone was documented along with insignificant postdialysis pain increment. This evidence will contribute toward considerations as to the safety of the use of oxycodone in dialysis patients in the future.

Relationships between oxycodone pharmacokinetics, central symptoms, and serum interleukin-6 in cachectic cancer patients.

Elevated serum proinflammatory cytokines are associated with the reduction of cytochrome P450 enzyme (CYP) activity. This study aimed to evaluate the oxycodone pharmacokinetics, central symptoms, and serum proinflammatory cytokines based on cachexia stage in cancer patients. Forty-seven cancer patients receiving extended-release oxycodone were enrolled. Predose plasma concentrations of oxycodone and its metabolites were normalized with the daily dose and body weight. The central symptoms and serum level of proinflammatory cytokines were investigated at each cachexia stage. The plasma concentrations of oxycodone in patients with cachexia and refractory cachexia were significantly higher than that in patients with precachexia. The metabolic ratio to noroxycodone in patients with cachexia was significantly lower than that in patients with precachexia. The patients with a higher cachexia stage had a higher serum level of interleukin-6 (IL-6), but not tumor necrosis factor-α and interleukin-1β. The serum IL-6 level was correlated with the plasma concentration of oxycodone and inversely with the metabolic ratio to noroxycodone. The incidence of somnolence was not associated with the plasma oxycodone concentration. In contrast, the cachexia stage and its associated serum IL-6 level were correlated with the incidence of somnolence. Cancer cachexia raised the plasma exposure of oxycodone through the reduction of CYP3A metabolic pathway. The reduction of CYP3A in cachectic cancer patients was associated with an elevation of serum IL-6. Although cachectic cancer patients with higher serum IL-6 levels had the symptom of somnolence, the alterations in oxycodone pharmacokinetics were not related to the incidence of symptom.

Postoperative oxycodone in breast cancer surgery: What factors associate with analgesic plasma concentrations?

Abstract Aims Parenteral oxycodone is increasingly used worldwide to manage perioperative pain. Oxycodone doses required for adequate analgesia vary significantly between individuals. Our study investigated whether an analgesic plasma concentration could be determined for oxycodone and which factors affect it. Methods 1000 women undergoing breast cancer surgery were recruited to the study. Demographic data were collected and their cold and heat pain sensitivity and anxiety scores were measured preoperatively. After surgery, rest and motion pain intensities were measured. Intravenous oxycodone was administered until the patients reported satisfactory pain relief (NRS &lt;4/10). At this point, plasma concentrations of oxycodone and its metabolites were determined. A second plasma sample for oxycodone deter-mination was taken when the patient requested a new dose of oxycodone. Genomic DNA was extracted from whole blood samples and the patients were genotyped for CYP2D6, CYP3A4 and CYP3A5 variants. Results The two oxycodone concentrations showed a strong correlation (r =0.84). The pain intensity measured during motion before oxycodone dosing correlated significantly with the plasma oxycodone concentration (geometric mean 35.3 ng/ml and CV % 66.4) required to achieve satisfactory analgesia (r = 0.38, p = 1.5 x 10-33). The most important factors associating with postoperative pain intensity were type of surgery (breast conserving or mastectomy with or without axillary clearance) and the age of the patient. Older patients reported lower pain scores and required smaller oxycodone concentrations for satisfactory analgesia. CYP2D6, CYP3A5 or CYP3A4 genotypes did not significantly affect the oxycodone concentrations, but CYP2D6 genotype significantly affected the formation of the metabolites oxymorphone and noroxymorphone. CYP3A4 and CYP3A5 genotypes did not affect the metabolite formation. Conclusions Our results indicate that the more pain the patient experiences postoperatively the greater her minimum plasma oxycodone concentration must be to achieve satisfactory analgesia. Type of surgery and age significantly affect postoperative pain intensity.

Is It Truly the Answer? Personalized Oxycodone Dosing Based on Pharmacogenetic Testing and the Corresponding Pharmacokinetics

Dear Editor, It is with great interest that we read the article by Linares and colleagues, “Personalized oxycodone dosing: using pharmacogenetic testing and clinical pharmacokinetics to reduce toxicity risk and increase effectiveness”, published in the April 2014 issue of Pain Medicine [1]. In this study, a randomized, crossover, double-blind, placebo-controlled investigation was conducted, with a total of 15 healthy male subjects phenotyped as CYP2D6 ultra-rapid metabolizer (UM), extensive metabolizer (EM), or poor metabolizer (PM) to obtain mean plasma oxycodone concentrations at each time point in each phenotype, and subsequently to be used to generate the phenotype-specific drug clearance parameter, in an attempt to “develop a frame for integrating pharmacogenetics with clinical pharmacokinetics for personalized oxycodone dosing based on a patient’s CYP2D6 phenotype.” The authors utilized a plethora of complicated computational formulae in advanced pharmacokinetics, and applied them to the subjects whose CYP2D6 polymorphisms were known, via genetic testing, to determine the target therapeutic plasma oxycodone concentrations, and finally determined the personalized oxycodone dose with the utilization of “phenotype-specific clinical pharmacokinetics” after repeated pharmacokinetic computations. The authors concluded that “By expressing a patient’s CYP2D6 phenotype pharmacokinetically, a clinician (at least theoretically) can improve the safety and efficacy of oxycodone and decrease the risk for iatrogenically induced overdose or death”. We respect the painstaking effort of the Linares and colleagues devoted to this highly technical 16-page work …

Plasma Concentration of Oxycodone and Pain during Hemodialysis in a Patient with Cancer

Pain is one of the most common problems in palliative medicine, and opioid therapy should be used adequately. Clinically, many cancer patients with severe renal dysfunction receive opioids for pain control. However, the pharmacokinetics of opioids during hemodialysis are not completely understood. We investigated the time course of the plasma concentration of oxycodone and pain during hemodialysis in a 55-year-old man using oxycodone for cancer pain. The patient’s plasma concentration of oxycodone decreased during hemodialysis, and increased after it ended. Conversely, his pain increased after the beginning of hemodialysis, and improved after it was finished. Additionally, our results did not show a relationship between the plasma concentration of oxycodone and his pain. Breakthrough pain occurred several times during hemodialysis irrespective of the plasma concentration of oxycodone. The decrease in plasma oxycodone during hemodialysis appeared to be caused by the removal of oxycodone by hemodialysis, and the later increase after hemodialysis appeared to be related to the redistribution of oxycodone. On the other hand, breakthrough pain during hemodialysis may be caused by hemodialysis itself, rather than due to the decrease of the plasma concentration of oxycodone, given that no relationship between the plasma concentration of oxycodone and pain could be identified. When building a strategy of pain management during hemodialysis, both the possibilities of a decrease in the plasma concentration of oxycodone by hemodialysis and the increase of pain by hemodialysis itself should be considered.

A Dose-Finding Study of Dexketoprofen in Patients Undergoing Laparoscopic Cholecystectomy: A Randomized Clinical Trial on Effects on the Analgesic Concentration of Oxycodone.

BackgroundDexketoprofen has been shown to provide efficient analgesia and an opioid-sparing effect after orthopedic surgery. In this dose-finding study, we evaluated the analgesic efficacy and opioid-sparing effect of dexketoprofen administered intravenously (i.v.) after laparoscopic cholecystectomy (LCC).MethodsTwenty-four patients undergoing LCC were randomized to receive dexketoprofen 10 or 50 mg i.v. 15 min before the end of the surgery. Subjects were provided with 0.2 mg/kg of oxycodone at anesthesia induction. In the recovery room, pain was assessed with an 11-point numerical rating scale (NRS; score of 0 = no pain, score of 10 = most severe pain) every 10 min. When the NRS score was ≥3/10 at rest or ≥5/10 at wound compression, a plasma sample was taken for analysis of oxycodone [to determine the minimum effective concentration (MEC)], its metabolites, and dexketoprofen. After that, subjects were titrated with oxycodone 2 or 3 mg i.v. every 10 min until the NRS score was <3/10 at rest and <5/10 at wound compression. At this point, a second plasma sample was taken for analysis of oxycodone [minimum effective analgesic concentration (MEAC)], its metabolites, and dexketoprofen.ResultsAt the onset of pain, the plasma oxycodone concentrations (MEC) were similar in the two groups: median 60 ng/mL (range 37–73) in the 10 mg group and median 52 ng/mL (range 24–79) in the 50 mg group. At the time of pain relief, the MEACs were 98 ng/mL (range 59–150) in the 10 mg group and 80 ng/mL (range 45–128) in the 50 mg group. The total doses of oxycodone needed to achieve pain relief were similar: 0.11 mg/kg (range 0–0.33) in the 10 mg group and 0.08 mg/kg (range 0–0.24) in the 50 mg group. Eleven subjects developed mild desaturation or a decreased respiratory rate after oxycodone titration.ConclusionIn the present double-blinded, randomized clinical trial, the need for a rescue opioid analgesic, oxycodone, was similar with the two dose levels of dexketoprofen—10 and 50 mg i.v.—after LCC.

Single‐ and multiple‐dose study to evaluate pharmacokinetics, safety and tolerability in healthy volunteers: A comparison of extended‐release oxycodone with sequestered naltrexone 40 mg twice daily to oxycontin 40 mg twice daily and extended‐release oxycodone with sequestered naltrexone 80 mg once daily

AbstractALO‐02 capsules (ALO‐02) contain pellets that consist of extended‐release oxycodone that surrounds sequestered naltrexone. The primary objective was to characterize the pharmacokinetics (PK) of oxycodone following single‐ and multiple‐dose oral administration of ALO‐02 40 mg BID in healthy volunteers. Secondary objectives were to characterize (1) the PK of oxycodone following single‐ and multiple‐dose administration of a comparator OxyContin (OXY‐ER) 40 mg BID as well as an alternate regimen of ALO‐02 80 mg QD, and (2) the safety and tolerability assessments. Healthy volunteers received three treatments on a background of oral naltrexone (50 mg). Noncompartmental PK parameters were calculated for oxycodone. All 12 subjects were male with a mean age (SD, range) of 44.6 years (7.6, 25–55). Single‐dose PK results for ALO‐02 indicate that median peak plasma oxycodone concentrations were reached by 12 hours compared to 4 hours for OXY‐ER. Compared to OXY‐ER, mean dose‐normalized, single‐dose Cmax values were approximately 27% and 23% lower for ALO‐02 40 mg BID and ALO‐02 80 mg QD treatments, respectively. Following multiple doses all treatments reached steady state by 3 days. At steady state, oxycodone peak‐to‐trough fluctuation was significantly lower for ALO‐02 BID versus OXY‐ER. Adverse events were consistent with opioid therapy. ALO‐02 40 mg BID treatment provided a PK profile appropriate for around‐the‐clock treatment of chronic pain.

Safety and pharmacokinetics of oxycodone DETERx administered intranasally in recreational opioid users

s / Drug and Alcohol Dependence 146 (2015) e118–e201 e163 middle school students described parental disapproval as a deterrent, high school students also cited friend disapproval as deterring use. Across all groups, thosewhohad not tried e-cigs described lack of “coolness” as an additional deterrent. Conclusions: This qualitative study indicated several reasons why youth initiated, abstained from and discontinued e-cigarettes. While there were some common themes across groups, different themes also emerged across the age groups. Understanding these factors may inform e-cig prevention messages. Financial Support: This work was supported by the National Institute on Drug Abuse grant P50DA009241. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.359 Safety and pharmacokinetics of oxycodone DETERx administered intranasally in recreational opioid users A. Kopecky1, Alison B. Fleming1, Patrick K. Noonan2 1 Collegium Pharmaceutical, Inc., Canton, MA, United States 2 PK Noonan Pharmaceutical Consulting, LLC, Williamsburg, VA, United States Aims: Oxycodone DETERx is a multi-particulate, abusedeterrent formulation designed to retain ER properties following common methods of tampering. The purpose of this study was to assess the safety and the pharmacokinetics (PK) of crushed DETERx capsule contents administered IN (DETERx IN) compared with 2 control treatments: immediate-release (IR) oxycodone powder administered IN (Oxy IN) and intact DETERx capsules administered orally (DETERx PO). Methods: Open-label, randomized, naltrexone-blocked, 3treatment, 3-period, crossover comparison study. Safety and PK of 40mg doses of DETERx IN, Oxy IN, and DETERx PO were compared innondependent, recreational opioid users experiencedwith IN administration (n=13). DETERx capsule contents were crushed using themost aggressive crushingmethod identified in previously conducted studies. Plasma samples were collected at pre-specified time points and analyzed using a LC–MS/MS method. PK parameters Cmax, AUCINF, TmaxandAbuseQuotient (AQ)were calculated. Safety assessments included treatment-emergent adverse events, vital signs, oxygen saturation and nasal cavity assessments. Results: Cmax LSMean ratio for DETERx IN relative to Oxy IN was 59.0%. Cmax LSMean ratio for DETERx IN relative to DETERx PO was 79.6%. DETERx IN and DETERx PO both had a median Tmax of 5.0h, longer than Oxy IN (3.0h). Oxy IN had the highest AQ value (42.5ng/ml/h); AQ values for DETERx IN and DETERx POwere similar (8.5 and 8.4ng/ml/h, respectively). AUCINF values were similar for all treatments. There weremore spontaneously reported nasalrelated AEs and a greater number of episodes of need to blow nose post insulation of crushed DETERx compared with Oxy. Conclusions: Crushing and snorting DETERx capsule contents produces relatively lower plasma concentrations of oxycodone compared with intact DETERx PO and Oxy IN, indicating that a concentration driven euphoric effect sought by drug abusers may not be achieved. Due to the higher number of nasal-related AEs, abusers may find DETERx less desirable. Financial Support: Collegium Pharmaceutical. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.360 A novel behavioral activation intervention for smoking cessation; mechanisms of change Catalina Kopetz1, Laura MacPherson2, Avery Mitchell 2, Alexandra HoustonLudlam2, Reinout W. Wiers3, Helle Larsen3 1 Psychology, Wayne State University, Detroit, MI, United States 2 Psychology, University of Maryland, College Park, MD, United States 3 Psychology, University of Amsterdam, Amsterdam,

A novel behavioral activation intervention for smoking cessation; mechanisms of change

s / Drug and Alcohol Dependence 146 (2015) e118–e201 e163 middle school students described parental disapproval as a deterrent, high school students also cited friend disapproval as deterring use. Across all groups, thosewhohad not tried e-cigs described lack of “coolness” as an additional deterrent. Conclusions: This qualitative study indicated several reasons why youth initiated, abstained from and discontinued e-cigarettes. While there were some common themes across groups, different themes also emerged across the age groups. Understanding these factors may inform e-cig prevention messages. Financial Support: This work was supported by the National Institute on Drug Abuse grant P50DA009241. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.359 Safety and pharmacokinetics of oxycodone DETERx administered intranasally in recreational opioid users A. Kopecky1, Alison B. Fleming1, Patrick K. Noonan2 1 Collegium Pharmaceutical, Inc., Canton, MA, United States 2 PK Noonan Pharmaceutical Consulting, LLC, Williamsburg, VA, United States Aims: Oxycodone DETERx is a multi-particulate, abusedeterrent formulation designed to retain ER properties following common methods of tampering. The purpose of this study was to assess the safety and the pharmacokinetics (PK) of crushed DETERx capsule contents administered IN (DETERx IN) compared with 2 control treatments: immediate-release (IR) oxycodone powder administered IN (Oxy IN) and intact DETERx capsules administered orally (DETERx PO). Methods: Open-label, randomized, naltrexone-blocked, 3treatment, 3-period, crossover comparison study. Safety and PK of 40mg doses of DETERx IN, Oxy IN, and DETERx PO were compared innondependent, recreational opioid users experiencedwith IN administration (n=13). DETERx capsule contents were crushed using themost aggressive crushingmethod identified in previously conducted studies. Plasma samples were collected at pre-specified time points and analyzed using a LC–MS/MS method. PK parameters Cmax, AUCINF, TmaxandAbuseQuotient (AQ)were calculated. Safety assessments included treatment-emergent adverse events, vital signs, oxygen saturation and nasal cavity assessments. Results: Cmax LSMean ratio for DETERx IN relative to Oxy IN was 59.0%. Cmax LSMean ratio for DETERx IN relative to DETERx PO was 79.6%. DETERx IN and DETERx PO both had a median Tmax of 5.0h, longer than Oxy IN (3.0h). Oxy IN had the highest AQ value (42.5ng/ml/h); AQ values for DETERx IN and DETERx POwere similar (8.5 and 8.4ng/ml/h, respectively). AUCINF values were similar for all treatments. There weremore spontaneously reported nasalrelated AEs and a greater number of episodes of need to blow nose post insulation of crushed DETERx compared with Oxy. Conclusions: Crushing and snorting DETERx capsule contents produces relatively lower plasma concentrations of oxycodone compared with intact DETERx PO and Oxy IN, indicating that a concentration driven euphoric effect sought by drug abusers may not be achieved. Due to the higher number of nasal-related AEs, abusers may find DETERx less desirable. Financial Support: Collegium Pharmaceutical. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.360 A novel behavioral activation intervention for smoking cessation; mechanisms of change Catalina Kopetz1, Laura MacPherson2, Avery Mitchell 2, Alexandra HoustonLudlam2, Reinout W. Wiers3, Helle Larsen3 1 Psychology, Wayne State University, Detroit, MI, United States 2 Psychology, University of Maryland, College Park, MD, United States 3 Psychology, University of Amsterdam, Amsterdam,