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Expert Opinion on Drug Delivery Jun 2019: To establish the first plasma and cerebrospinal fluid (CSF) oxycodone population pharmacokinetic (PopPK) model after epidural (EPI) and intravenous (IV) oxycodone... (Comparative Study)
Comparative Study Randomized Controlled Trial
: To establish the first plasma and cerebrospinal fluid (CSF) oxycodone population pharmacokinetic (PopPK) model after epidural (EPI) and intravenous (IV) oxycodone administration. : The study was conducted with 30 female subjects undergoing elective gynecological surgery with epidural analgesia. A parallel single dose of EPI oxycodone with IV placebo (EPI group; n = 18) or IV oxycodone with EPI placebo (IV group; n = 12) was administered. An epidural catheter for drug administration was placed at T12/L1 and a spinal catheter for CSF sampling at L3/4. Plasma and CSF for oxycodone analysis were frequently collected. A PopPK model was built using the NONMEM software package. : Plasma and CSF oxycodone concentrations were evaluated using separate central plasma and CSF compartments and separate peripheral plasma and CSF compartments. Epidural space served as a depot compartment with transfer to both the plasma and CSF central compartments. The population parameters for plasma clearance and apparent distribution volumes for central and peripheral compartments for plasma and CSF were 37.4 L/h, 90.2 L, 68.9 L, 0.035 L (fixed based on literature), and 0.039 L, respectively. : A PopPK model was developed and found to precisely and accurately describe oxycodone time-concentration data in plasma and CSF.
Topics: Administration, Intravenous; Adult; Double-Blind Method; Epidural Space; Female; Humans; Middle Aged; Oxycodone
PubMed: 31092024
DOI: 10.1080/17425247.2019.1618267 -
Journal of Opioid Management 2018The role of analgesia is crucial in the management of postoperative pain. Different combinations of oral analgesics have been proposed in the past. The... (Review)
Review
BACKGROUND
The role of analgesia is crucial in the management of postoperative pain. Different combinations of oral analgesics have been proposed in the past. The oxycodone/naloxone (OXN) combination is a recent addition and is being used by different surgical specialties. The aim of our study was to clarify the possible role, advantages, and disadvantages of OXN in the pain management of surgical patients.
METHOD
The authors retrieved the included studies after performing a systematic search in PubMed and Scopus.
RESULTS
Ten studies (six randomized controlled trials, three retrospective studies, and a prospective study) were eligible for inclusion in this review. In total, 1,996 patients were included. Six studies reported on orthopedic procedures while four studies referred to colorectal, gynecologic, cardiac, and thoracic surgery procedures, respectively. The analgesic effect of OXN was evaluated in nine out of 10 studies, where OXN showed superiority only in two out of nine studies. Postoperative bowel function was evaluated in seven out of 10 studies. Patients treated with OXN did not show any significant differences in bowel function when compared to control groups. No superiority was found regarding the possible adverse events.
CONCLUSION
Analgesia is crucial to postoperative recovery. Pain control can be achieved a combination of different analgesics, including OXN. This oral analgesic combination can have the potential to minimize side effects, such as opioid-induced constipation and optimize the recovery period.
Topics: Drug Combinations; Humans; Naloxone; Oxycodone; Pain, Postoperative
PubMed: 29508896
DOI: 10.5055/jom.2018.0429 -
Scandinavian Journal of Pain Apr 2021Opioids are often used in treatment of severe pain, although many patients experience gastrointestinal side-effects like constipation. The aim of the current study was... (Randomized Controlled Trial)
Randomized Controlled Trial
Although tapentadol and oxycodone both increase colonic volume, tapentadol treatment resulted in softer stools and less constipation: a mechanistic study in healthy volunteers.
OBJECTIVES
Opioids are often used in treatment of severe pain, although many patients experience gastrointestinal side-effects like constipation. The aim of the current study was to investigate changes in colonic volume, as the result of both colonic motility and fluid transport, in healthy volunteers during opioid treatment with tapentadol as compared with oxycodone and placebo.
METHODS
In a randomized, double-blind, cross-over study, 21 healthy male volunteers were administered equianalgesic dosages of oral tapentadol (50 mg bid), oxycodone (10 mg bid) or corresponding placebo for 14 days. Segmental colonic volumes were quantified using T2-weighted magnetic resonance images, and gastrointestinal side-effects were assessed with questionnaires.
RESULTS
Total colonic volume increase during treatment was higher during tapentadol and oxycodone treatment (median 48 and 58 mL) compared to placebo (median -14 mL, both p≤0.003). Tapentadol (and placebo) treatment resulted in more bowel movements (both p<0.05) and softer stool consistency as compared with oxycodone (both p<0.01). Only oxycodone treatment was associated with increased constipation, straining during defecation, and tiredness (all p≤0.01). The colonic volume increase during treatment was directly associated with softer stools during tapentadol treatment (p=0.019).
CONCLUSIONS
Tapentadol treatment increased colonic volume without leading to harder stools, likely as the opioid sparing effects result in less water absorption from the gut lumen. Oxycodone treatment also increased colonic volume, but with a simultaneous increase in stool dryness and gastrointestinal and central nervous system side-effects. The results confirm that tapentadol treatment may be advantageous to oxycodone regarding tolerability to pain treatment.
Topics: Colon; Constipation; Cross-Over Studies; Healthy Volunteers; Humans; Male; Oxycodone; Tapentadol
PubMed: 33606931
DOI: 10.1515/sjpain-2020-0151 -
Medical Science Monitor : International... Mar 2021BACKGROUND The aim of the present study was to evaluate the effects of different doses of oxycodone during endoscopic injection sclerotherapy (EIS) for esophageal...
BACKGROUND The aim of the present study was to evaluate the effects of different doses of oxycodone during endoscopic injection sclerotherapy (EIS) for esophageal varices with painless sclerosing agents. MATERIAL AND METHODS A total of 119 patients were randomly divided into 3 groups: Group A, midazolam and 0.075 mg/kg oxycodone (n=40); Group B, midazolam and 0.1 mg/kg oxycodone (n=40); and Group C, midazolam and 0.125 mg/kg oxycodone (n=39). The main observation index was the incidence of body movement during the perioperative period. The secondary indices were additional propofol usage; postoperative analgesic usage; other adverse effects, such as hypoxia, myoclonus, and cough; and satisfaction scores for surgeons and patients. RESULTS The incidence rates for body movement during the perioperative period in groups A, B, and C were 33%, 13%, and 0, respectively (P<0.001). The satisfaction scores for surgeons and patients were highest in Group C (0.125 mg/kg oxycodone). The incidence rates for hypoxia before EIS were 15%, 8%, and 33% (P=0.026) and during EIS were 23%, 3%, and 0% (P<0.001), respectively. There were no significant between-group differences with respect to other adverse effects. CONCLUSIONS The ideal dose of oxycodone for perioperative analgesia during EIS for esophageal varices is 0.125 mg/kg.
Topics: Adult; China; Dose-Response Relationship, Drug; Endoscopy; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Injections; Liver Cirrhosis; Male; Midazolam; Middle Aged; Oxycodone; Perioperative Period; Prospective Studies; Sclerosing Solutions; Sclerotherapy
PubMed: 33727522
DOI: 10.12659/MSM.929111 -
The Journal of Pharmacology and... May 2018Heroin and oxycodone abuse occurs over a wide range of drug doses and by various routes of administration characterized by differing rates of drug absorption. The...
Heroin and oxycodone abuse occurs over a wide range of drug doses and by various routes of administration characterized by differing rates of drug absorption. The current study addressed the efficacy of a heroin vaccine [morphine hapten conjugated to keyhole limpet hemocyanin (M-KLH)] or oxycodone vaccine [oxycodone hapten conjugated to keyhole limpet hemocyanin (OXY-KLH)] for reducing drug distribution to brain after intravenous heroin or oxycodone, or subcutaneous oxycodone. Rats immunized with M-KLH or keyhole limpet hemocyanin (KLH) control received an intravenous bolus dose of 0.26 or 2.6 mg/kg heroin. Vaccination with M-KLH increased retention of heroin and its active metabolites 6-acetylmorphine (6-AM) and morphine in plasma compared with KLH controls, and reduced total opioid (heroin + 6-AM + morphine) distribution to brain but only at the lower heroin dose. Immunization also protected against respiratory depression at the lower heroin dose. Rats immunized with OXY-KLH or KLH control received 0.22 or 2.2 mg/kg oxycodone intravenously, the molar equivalent of the heroin doses. Immunization with OXY-KLH significantly reduced oxycodone distribution to brain after either oxycodone dose, although the magnitude of effect of immunization at the higher oxycodone dose was small (12%). By contrast, vaccination with OXY-KLH was more effective when oxycodone was administered subcutaneously rather than intravenously, reducing oxycodone distribution to brain by 44% after an oxycodone dose of 2.3 mg/kg. Vaccination also reduced oxycodone-induced antinociception. These data suggest that the efficacy of OXY-KLH and M-KLH opioid vaccines is highly dependent upon opioid dose and route of administration.
Topics: Animals; Brain; Dose-Response Relationship, Drug; Drug Administration Routes; Heroin; Male; Opioid-Related Disorders; Oxycodone; Rats; Vaccines
PubMed: 29535156
DOI: 10.1124/jpet.117.247049 -
Movement Disorders : Official Journal... Sep 2015Levodopa and dopamine agonists have been the main treatment for restless legs syndrome during the past decades. Although their efficacy has been well documented over the... (Meta-Analysis)
Meta-Analysis Review
Levodopa and dopamine agonists have been the main treatment for restless legs syndrome during the past decades. Although their efficacy has been well documented over the short term, long-term dopaminergic treatment is often complicated by augmentation, loss of efficacy, and other side effects. Recent large randomized controlled trials provide new evidence for the efficacy of high-potency opioids and α2δ ligands, and several post hoc analyses, meta-analyses, algorithms, and guidelines have been published, often with a specific focus, for example, on augmentation, or on management of restless legs syndrome during pregnancy. Several new contributions to understanding the pathophysiology of restless legs syndrome have been published, but at this time, whether they will have an impact on treatment possibilities in the future cannot be estimated.
Topics: Diet Therapy; Dopamine Agents; Drug Combinations; Humans; Iron; Naloxone; Oxycodone; Randomized Controlled Trials as Topic; Restless Legs Syndrome
PubMed: 26371624
DOI: 10.1002/mds.26381 -
Scientific Reports Aug 2023Oxycodone is one of the most widely prescribed and misused opioid painkillers in the United States. Evidence suggests that biological sex and hormonal status can impact...
Oxycodone is one of the most widely prescribed and misused opioid painkillers in the United States. Evidence suggests that biological sex and hormonal status can impact drug reward in humans and rodents, but the extent to which these factors can influence the rewarding effects of oxycodone is unclear. The purpose of this study was to utilize place conditioning to determine the effects of sex and female hormonal status on the expression of oxycodone conditioned reward in rats. Gonadally intact adult Sprague-Dawley male and female rats were used to test: (1) whether both sexes express conditioned reward to oxycodone at similar doses, (2) the impact of conditioning session length on oxycodone conditioned reward expression in both sexes, and (3) the influence of female estrous cycle stage on oxycodone conditioned reward expression. Both sexes expressed conditioned reward at the same doses of oxycodone. Increasing the length of conditioning sessions did not reveal an effect of sex and resulted in lower magnitude conditioned reward expression. Importantly however, female stage of estrous cycle significantly influenced oxycodone conditioned reward expression. These results suggest that female hormonal status can impact the rewarding effects of opioids and thus have important implications for prescription opioid treatment practices.
Topics: Adult; Humans; Rats; Female; Male; Animals; Rats, Sprague-Dawley; Oxycodone; Analgesics, Opioid; Estrous Cycle; Reward
PubMed: 37626154
DOI: 10.1038/s41598-023-40971-3 -
Pharmacology, Biochemistry, and Behavior Oct 2021Recent data suggest that glial cells may be involved in the analgesic effects and abuse liability of opioids. Preclinical studies have demonstrated that... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Recent data suggest that glial cells may be involved in the analgesic effects and abuse liability of opioids. Preclinical studies have demonstrated that mu-opioid-receptor-selective agonists, such as oxycodone, activate glia and increase the release of cytokines, causing a suppression of opioid-induced analgesic effects. Preclinical studies also show that certain medications, such as the broad-spectrum tetracycline antibiotic minocycline, inhibit opioid-induced glial activation and thereby enhance the analgesic effects of opioids. Importantly, minocycline reduces the rewarding effects of opioids at the same doses that it enhances opioid-induced analgesia.
AIMS
The purpose of the present study was to assess the effects of acute administration of minocycline on the subjective, physiological, and analgesic effects of oxycodone in human research volunteers.
DESIGN
This study was a within-subject, randomized, double-blind outpatient study. Participants completed five separate sessions in which they received 0, 100, or 200 mg minocycline (MINO) simultaneously with either 0 or 40 mg oxycodone (OXY). The subjective, physiological, and analgesic effects of OXY were measured before and repeatedly after drug administration.
SETTINGS AND PARTICIPANTS
Participants were between 21 and 45 years of age, non-treatment seeking, non-dependent recreational opioid users (N = 12). This study was conducted between 2013 and 2014 at the New York State Psychiatric Institute in New York, NY.
FINDINGS
MINO 100 and 200 mg were safe and well-tolerated in combination with OXY 40 mg. MINO 200 mg administered with OXY 40 mg attenuated OXY-induced positive subjective effects such as "Good Effect" and "Liking" compared to OXY alone. MINO did not alter the physiological or analgesic effects of OXY.
CONCLUSIONS
MINO may attenuate the abuse liability of mu-opioid-receptor-selective agonists.
Topics: Adult; Analgesia; Analgesics, Opioid; Anti-Bacterial Agents; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Microglia; Middle Aged; Minocycline; New York; Opioid-Related Disorders; Oxycodone; Reward; Young Adult
PubMed: 34298029
DOI: 10.1016/j.pbb.2021.173241 -
Neuropharmacology Nov 2023Chronic opioid use disturbs circadian rhythm and sleep, encouraging opioid use and relapse. The orexin (OX) system is recruited by opioids and regulates physiological...
Chronic opioid use disturbs circadian rhythm and sleep, encouraging opioid use and relapse. The orexin (OX) system is recruited by opioids and regulates physiological processes including sleep. Dual OX receptor antagonists (DORAs), developed for insomnia treatment, may relieve withdrawal-associated sleep disturbances. This study investigated whether DORA-12, a recently developed DORA, reduces physiological activity disturbances during oxycodone abstinence and consequently prevents oxycodone-seeking behavior. Male and female Wistar rats were trained to intravenously self-administer oxycodone (0.15 mg/kg, 21 sessions; 8 h/session) in the presence of a contextual/discriminative stimulus (S). The rats were subsequently housed individually (22 h/day) to monitor activity, food and water intake. They received DORA-12 (0-30 mg/kg, p.o.) after undergoing daily 1-h extinction training (14 days). After extinction, the rats were tested for oxycodone-seeking behavior elicited by the S. Hypothalamus sections were processed to assess oxycodone- or DORA-12-associated changes to the OX cell number. In males, oxycodone-associated increases in activity during the light-phase, reinstatement, and decreases in the number of OX cells observed in the vehicle-treated group were not observed with DORA-12-treatment. Oxycodone-associated increases in light-phase food and water intake were not observed by day 14 of 3 mg/kg DORA-12-treatment and dark-phase water intake was increased across treatment days. In females, OX cell number was unaffected by oxycodone or DORA-12. Three and 30 mg/kg DORA-12 increased females' day 7 dark-phase activity and decreased reinstatement. Thirty mg/kg DORA-12 reduced oxycodone-associated increases in light-phase food and water intake. The results suggest that DORA-12 improves oxycodone-induced disruptions to physiological activities and reduces relapse.
Topics: Female; Rats; Male; Animals; Oxycodone; Analgesics, Opioid; Orexin Receptor Antagonists; Rats, Sprague-Dawley; Rats, Wistar; Orexin Receptors; Self Administration
PubMed: 37579870
DOI: 10.1016/j.neuropharm.2023.109685 -
Behavioural Pharmacology Sep 2022The prescription opioid oxycodone is widely used for the treatment of pain in humans. Oxycodone misuse is more common among people with an anxiety disorder than those...
The prescription opioid oxycodone is widely used for the treatment of pain in humans. Oxycodone misuse is more common among people with an anxiety disorder than those without one. Therefore, oxycodone might be misused for its anxiolytic properties. We investigated if oxycodone affects anxiety-like behavior in adult male and female rats. The rats were treated with oxycodone (0.178, 0.32, 0.56, or 1 mg/kg), and anxiety-like behavior was investigated in the elevated plus-maze test. Immediately after the elevated plus-maze test, a small open field test was conducted to determine the effects of oxycodone on locomotor activity. In the elevated plus-maze test, oxycodone increased the percentage of time spent on the open arms, the percentage of open arm entries, time on the open arms, open arm entries, and the distance traveled. The males treated with vehicle had a lower percentage of open arm entries than the females treated with vehicle, and oxycodone treatment led to a greater increase in the percentage of open arm entries in the males than females. Furthermore, the females spent more time on the open arms, made more open arm entries, spent less time in the closed arms, and traveled a greater distance than the males. In the small open field test, treatment with oxycodone did not affect locomotor activity or rearing. Sex differences were observed; the females traveled a greater distance and displayed more rearing than the males. In conclusion, oxycodone decreases anxiety-like behavior in rats, and oxycodone has a greater anxiolytic-like effect in males than females.
Topics: Animals; Anti-Anxiety Agents; Anxiety; Behavior, Animal; Elevated Plus Maze Test; Female; Humans; Locomotion; Male; Maze Learning; Oxycodone; Rats
PubMed: 35947068
DOI: 10.1097/FBP.0000000000000690