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At least 757 records · Page 42Linked to original sources
PubMed2005

Opioid rotation from morphine to fentanyl in delirious cancer patients: an open-label trial.

Although recent studies suggest that opioid rotation could be an effective treatment strategy for morphine-induced delirium, there have been no prospective studies to investigate the treatment effects of opioid rotation using fentanyl. The primary aim of this study was to clarify the efficacy of opioid rotation from morphine to fentanyl in symptom palliation of morphine-induced delirium. Twenty-one consecutive cancer patients with morphine-induced delirium underwent opioid rotation to fentanyl. Physicians recorded the symptom severity of delirium (the Memorial Delirium Assessment Scale, MDAS), pain, and other symptoms (categorical verbal scale from 0: none to 3: severe) and the Schedule for Team Assessment Scale (STAS) (from 0: none to 4: extreme); and performance status at the time of study enrollment and three and seven days after. Of 21 patients recruited, one patient did not complete the study. In the remaining 20 patients, morphine was substituted with transdermal fentanyl in 9 patients and parenteral fentanyl in 11 patients. Total opioid dose increased from 64 mg oral morphine equivalent/day (Day 0) to 98 mg/day (Day 7), and the median increase in total opioid dose was 42%. Treatment success, defined as an MDAS score below 10 and pain score of 2 or less, was obtained in 13 patients on Day 3 and 18 patients on Day 7. The mean MDAS score significantly decreased from 14 (Day 0) to 6.4 and 3.6 (Days 3 and 7, respectively, P < 0.001). Pain scores significantly decreased from 2.2 (Day 0) to 1.3 and 1.1 on the categorical verbal scale (Days 3 and 7, respectively, P < 0.001); from 2.6 (Day 0) to 1.6 and 1.3 on the STAS (Days 3 and 7, respectively, P < 0.001). Symptom scores of dry mouth, nausea, and vomiting significantly decreased, and performance status significantly improved. Opioid rotation from morphine to fentanyl may be effective in alleviating delirium and pain in cancer patients with morphine-induced delirium.

Aged↗
PubMed2005

Does the use of fentanyl in epidural solutions for postthoracotomy pain management in neonates affect surgical outcome?

BACKGROUND/PURPOSE: Continuous epidural analgesia is routinely used to manage pain in infants undergoing resection of a congenital cystic adenomatoid malformation (CCAM) of the lung. Our aim was to determine if there is a difference in the length of stay (LOS), supplemental analgesic requirements, pain control, and the incidence of adverse respiratory events in infants receiving the 2 standard epidural solutions commonly used: bupivacaine 0.1% and bupivacaine 0.1% with fentanyl 2 to 5 microg/mL. METHODS: We retrospectively reviewed the charts of infants who received epidural infusions containing bupivacaine 0.1% (n = 18) and bupivacaine 0.1% with fentanyl 2 to 5 microg/mL (n = 10) after CCAM resection during a 12-month period. LOS, rescue opioid, and nonopioid analgesic use, incidence of respiratory depression, and pain scores were recorded. RESULTS: The LOS in patients receiving fentanyl in their epidural solution was 1 day longer than those receiving plain bupivacaine (median 4 vs 3 days, respectively). Nonopioid analgesic and rescue opioid use was greater in patients who did not have fentanyl in their epidural solutions. Pain ratings were not significantly different. The incidence of respiratory depression was greater in patients receiving epidural infusions containing fentanyl (50% vs 17%, respectively). CONCLUSION: The addition of fentanyl to epidural infusions of bupivacaine in infants undergoing thoracotomy for resection of CCAM may prolong recovery and increase the incidence of adverse respiratory events without providing a significant analgesic benefit.

Adjuvants, Anesthesia↗
PubMed2004

Prevention of fentanyl-induced delayed pronociceptive effects in mice lacking the protein kinase Cgamma gene.

It has recently been reported in several nociceptive models of rats that the antinociceptive effect of fentanyl, an opioid analgesic widely used in the management of per-operative pain, was followed by paradoxical delayed hyperalgesia dependent on N-methyl-D-aspartate (NMDA) mechanisms. Events upstream of the NMDA receptor, especially the activation of the protein kinase Cgamma (PKCgamma), have been involved in the persistence of pain states associated with central sensitisation. In order to evaluate the contribution of the PKCgamma in early and delayed fentanyl nociceptive responses, we studied these effects in knock-out mice deficient in such a protein. We found that fentanyl antinociception was followed by the spontaneous appearance of prolonged hyperalgesia in the paw pressure and formalin tests, and allodynia in the Von Frey paradigm. In PKCgamma deficient mice, an enhancement of the early fentanyl antinociceptive effects was observed, as well as a complete prevention of the fentanyl delayed hyperalgesic/allodynic effects. Finally, naloxone administration in mice that had recovered their pre-fentanyl nociceptive threshold, precipitated hyperalgesia/allodynia in wild-type but not in mutant mice. This study identifies the PKCgamma as a key element that links opioid receptor activation with the recruitment of opposite systems to opioid analgesia involved in a physiological compensatory pain enhancement.

Animals↗
PubMed2004

Relative analgesic potency of fentanyl and sufentanil during intermediate-term infusions in patients after long-term opioid treatment for chronic pain.

Sufentanil, a potent mu-opioid agonist, historically has not been been given systemically to treat chronic pain. An implantable, fixed-rate osmotic pump that delivers sufentanil subcutaneously is being developed for this purpose. In that transdermal fentanyl may be a useful intermediary to estimate the appropriate sufentanil dose before implant, accurate information is needed about the relative analgesic potency of sufentanil and fentanyl during continuous infusion. To determine this relative potency, we administered these drugs to opioid-treated chronic pain patients using a target-controlled infusion (TCI). Sixty-three patients with stable chronic pain and daily oral opioid requirements equivalent to 100-1000 mg of morphine received TCI of fentanyl and sufentanil, each for a minimum of 16 h. Drug administration was double-blind and the order of administration was randomly assigned. Target concentration was changed until the patient reported that analgesia was adequate (defined as a pain level equal to or better than baseline). Seven patients did not complete the infusion and protocol violations invalidated data for 15 patients. For the remaining 41 patients, target concentrations associated with adequate analgesia were achieved for both sufentanil and fentanyl. The median value for the equianalgesic concentration ratio (steady-state fentanyl infusion to steady-state sufentanil infusion) was 7.5; mean potency ratio was 7.44 (95% confidence interval 6.8-8.2). During titrated, intermediate-term infusions in patients previously treated with opioids for chronic pain, sufentanil is approximately 7.5 times as potent as fentanyl.

Adult↗
PubMed2004

Subanalgesic doses of dexketoprofen and HCT-2037 (nitrodexketoprofen) enhance fentanyl antinociception in monoarthritic rats.

Subanalgesic doses of the non-steroidal antiinflammatory drugs (NSAID) dexketoprofen trometamol and nitroparacetamol (NCX-701) enhance mu-opiate fentanyl effect in acute nociception. It is not known if a similar combination of drugs is effective in situations of spinal cord sensitization. The aim of this study was to assess if the enhancement of fentanyl antinociception can be observed in carrageenan-induced monoarthritis, when combined with dexketoprofen (DKT) or nitrodexketoprofen (HCT-2037). Withdrawal reflexes were recorded as single motor units in male Wistar rats anesthetized with alpha-chloralose. Fentanyl was studied alone and in the presence of 0.4, 0.8 micromol/kg of DKT or 0.3 micromol/kg of HCT-2037. In responses to noxious mechanical stimulation, the ID50 of fentanyl was enhanced twofold by 0.8 micromol/kg DKT and more than fourfold by HCT-2037 and no significant recovery was observed 45 min later. DKT 0.4 micromol/kg was, however, very little effective. The opioid antagonist naloxone did not reverse the effect. Enhancement of fentanyl effect on wind-up was only observed with HCT-2037 but not with DKT. We conclude that the combined administration of subanalgesic doses of dexketoprofen derivatives, specially its nitroderivative, and the mu-opiate fentanyl is an effective antinociceptive therapy in situations of articular inflammation involving a naloxone-independent mechanism of action.

Analgesics↗
PubMedDate not supplied

Fentanyl iontophoretic transdermal system for acute-pain management after orthopedic surgery: a comparative study with morphine intravenous patient-controlled analgesia.

BACKGROUND AND OBJECTIVES: The fentanyl HCl iontophoretic transdermal system (ITS) has been demonstrated in clinical trials to be safe and effective for acute-pain management after several types of major surgery. The current study compared the efficacy, safety, and convenience of fentanyl ITS with morphine intravenous patient-controlled analgesia (IV PCA) for acute-pain management after unilateral total-hip replacement (THR). METHODS: In this multicenter (52 sites), randomized, open-label, active-controlled, phase IIIb study, patients (n = 799) received fentanyl ITS (40 mug fentanyl [10-minute infusion/lockout], up to 6 doses/h) or morphine IV PCA (1-mg morphine bolus [5-minute lockout], up to 10 mg/h) after unilateral THR. The primary efficacy measure was success ratings ("excellent" or "good") on the patient global assessment (PGA) of the method of pain control in the first 24 hours. Pain intensity and adverse events were also assessed. RESULTS: The PGA success ratings (83.0% v 82.2%; difference = 0.9%; 95% CI: -4.4% to 6.1%) and the mean last pain-intensity scores (3.0 v 3.0; difference = 0.0; 95% CI: -0.33 to 0.33) in the first 24 hours were statistically equivalent between fentanyl ITS and morphine IV PCA groups, respectively. The incidence of adverse events was similar between the groups. CONCLUSIONS: Results of this study demonstrate fentanyl ITS and a standard regimen of morphine IV PCA were comparable methods of pain control for management of acute postoperative pain after THR, on the basis of the PGA success ratings and pain intensity in the first 24 hours of treatment.

Administration, Cutaneous↗
PubMedDate not supplied

Effect of addition of various doses of fentanyl intrathecally to 0.5% hyperbaric bupivacaine on perioperative analgesia and subarachnoid-block characteristics in lower abdominal surgery: a dose-response study.

BACKGROUND: The purpose of this randomized, double-blind, placebo-controlled trial is to study the effect of adding various doses of fentanyl to 2.2 mL of bupivacaine (0.5% hyperbaric), for spinal anesthetic in non-obstetric population undergoing superficial lower abdominal surgery (hernia repair). METHODS: A population of 60 patients belonging to ASA classes I and II, scheduled for elective inguinal hernia repair, were randomized to receive a spinal anesthetic with 2.2 mL of bupivacaine (0.5% hyperbaric) and saline (control group), or fentanyl 10, 20, 30, or 40 microg. The volume of injected drug was kept constant at 3 mL by adding preservative-free saline for blinding purposes. Subarachnoid block characteristics, drug-related side effects, and postoperative analgesia requirements were assessed and recorded. RESULTS: Significant improvement in quality and duration of analgesia occurred in treatment groups (receiving fentanyl and bupivacaine) compared with the control group (saline and bupivacaine) (P < .05). However, no improvement in analgesia occurred when the dose of fentanyl added was increased from 10 to 20, 30, or 40 microg. CONCLUSIONS: The data suggest that in a non-obstetric population receiving spinal anesthetic for superficial lower abdominal surgery (hernia repair), addition of 10 microg fentanyl to bupivacaine 0.5% (hyperbaric) significantly improves the quality and duration of analgesia. No further advantage occurs if the dose of fentanyl is increased up to 40 mug.

Abdomen↗
PubMed2006

Regional differences in transdermal penetration of fentanyl through equine skin.

The rate and regional differences for the penetration of fentanyl through equine skin was investigated in vitro using a commercial transdermal therapeutic system (TTS) or 'patch'. Skin collected from the thorax, groin and leg (dorsal metacarpal) regions of five horses was placed in diffusion cells and a fentanyl TTS applied to each skin sample. Drug penetration through each skin sample over 48 h measured using high performance liquid chromatography (HPLC). Cumulative penetration (microg/cm2) was plotted against time (h) and used to regress the steady state flux (microg/cm2/h) of fentanyl through each skin site. Results showed similar fluxes for both the thorax (2.32+/-0.17 microg/cm2/h and groin (2.21+/-0.11 (microg/cm2/h) regions, but significantly lower flux (P=<0.05) for the leg region (1.56+/-0.120 microg/cm2/h. Interestingly, there was a significantly longer lag time for the penetration of fentanyl through the groin region (7.87+/-0.51 h) compared to the other two sites (5.66+/-0.97 h and 5.75+/-0.43 h for the thorax and leg regions respectively). The results suggest that a fentanyl TTS applied to the leg region may have a small but significantly lower amount of fentanyl available systemically, compared to patches applied to the thorax or groin regions, which may affect the level of analgesia subsequently achieved in the horse.

Administration, Cutaneous↗
PubMed2005

Effectiveness of transdermal fentanyl patch for treatment of acute pain due to oral mucositis in patients receiving stem cell transplantation.

The current study was performed to evaluate the effectiveness and safety of transdermal therapeutic system (TTS) fentanyl in the management of acute pain due to oral mucositis in patients receiving stem cell transplantation. A cohort of consecutive patients with painful oral mucositis were enrolled. Initially, 25 microg/h of TTS fentanyl was administered for the treatment of oral mucositis pain. The pain score, based on a visual analogue scale, and mood and quality of sleep as determined by EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, Cancer 30), were all recorded before the treatment, then 2, 6, and 10 days later. Twenty-two patients with hematologic malignancies were enrolled. Three patients were excluded from the response assessment, as their TTS fentanyl treatment was stopped owing to related complaints, including severe dizziness, severe vomiting, and an extensive body rash. The total duration of the treatment was 8 days (range, 6-15 days) and the total amount of TTS fentanyl administered per patient was 2.21 at 25 microg/h and 0.63 at 50 microg/h. Six (31.6%) of the remaining 19 patients required an escalated dose of TTS fentanyl at 50 mug/h. The mean pain scores before treatment and 2, 6, and 10 days later were 6.68, 5.17, 3.42, and 2.13, respectively (P < .001). Eight (42.1%) and seven (36.8%) patients experienced improved sleep and mood after treatment, respectively. The TTS fentanyl was effective in both relieving oral mucositis pain with an excellent tolerability and improving the quality of life for hematological patients receiving high-dose chemotherapy with stem cell transplantation.

Adolescent↗
PubMed1997

Possible involvement of multiple cytochrome P450S in fentanyl and sufentanil metabolism as opposed to alfentanil.

Fentanyl, sufentanil, and alfentanil are commonly used as opioid analgesics. Alfentanil clearance has previously been shown to exhibit an important interindividual variability, which was not observed for fentanyl or sufentanil. Differences in pharmacokinetic parameters of alfentanil have previously been associated with the wide distribution of CYP3A4, the only known hepatic cytochrome P450 monooxygenase (CYP) involved in the conversion of alfentanil to noralfentanil. Little is known about the involvement of CYP enzymes in the oxidative metabolism of fentanyl and sufentanil. Microsomes prepared from different human liver samples were compared for their abilities to metabolize fentanyl, sufentanil and alfentanil, and it was found that disappearance of the three substrates was well correlated with immunoreactive CYP3A4 contents but not with other CYPs, including CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2D6 and CYP2E1. Specific known inhibitors of CYP enzymes gave similar results, whereas the use of recombinant human CYP enzymes expressed in yeast provided information about the possible involvement of other CYPs than CYP3A4 in the biotransformation of fentanyl and sufentanil. The possible in vivo interaction of fentanyl and sufentanil with other drugs catalyzed by CYP3A4 is also discussed.

Alfentanil↗
PubMed1996

Comparison of continuous infusion of fentanyl to bolus dosing in neonates after surgery.

OBJECTIVE: Concern about respiratory depression may lead to underuse of postoperative narcotic analgesia in neonates. The authors compared continuous infusion of fentanyl with bolus dosing in infants after surgery to determine whether continuous infusion is associated with less respiratory depression. STUDY DESIGN: In the first phase of the study, 16 patients were randomly assigned to receive fentanyl by continuous infusion (C) or bolus dosing every 2 hours (B) in a double-blinded trial. Respiratory events were recorded. An observational pain score and saliva for cortisol concentration were obtained 2, 8, and 24 hours after beginning treatment to compare efficacy of pain control. In the second phase, 20 additional patients received fentanyl by continuous infusion in an unblinded fashion, with the same data collection, to more accurately determine the incidence of respiratory events. RESULTS: In phase 1, apnea occurred in eight of nine B patients (89%) compared with one of seven C patients (14%; P < .009), prompting termination of the randomized trial. The incidence of apnea or significant respiratory depression in the next 20 patients (phase 2) who received fentanyl by continuous infusion was 25% (5 of 20; P < .01 v B). Episodes of apnea in B patients required significantly more intervention than episodes in C patients (P < .01). However, in phase 2, more patients remained intubated and ventilated than in phase 1. Pain scores and salivary cortisol concentrations decreased over the 24-hour study period and were similar in B and C patients during both phases of the study. CONCLUSION: Continuous infusion of fentanyl at the doses studied is associated with pain control similar to that with bolus dosing at regular intervals. Although episodes of respiratory depression were less severe and less frequent for C patients, there may be an increased need for ventilator support with continuous infusion of fentanyl to achieve acceptable pain control. Providing adequate pain control to neonates in the immediate postoperative period remains a challenge.

Analgesics, Opioid↗
PubMed2002

Effects of agmatine on the escalation of intravenous cocaine and fentanyl self-administration in rats.

Escalation of drug intake reliably occurs when animals are allowed extended self-administration access. As a form of plasticity, escalation of drug intake may be accompanied by neuroadaptive changes that are related to the transition from controlled use to addiction. The purpose of the present experiment was to examine the effects of agmatine (decarboxylated L-arginine) on the escalation of intravenous (iv) fentanyl and cocaine self-administration in rats. Subjects were allowed 12 h of daily access to fentanyl (2.5 microg/kg) or cocaine (0.2 mg/kg) under a fixed-ratio (FR) 1 schedule of reinforcement for 30 days. Animals self-administering fentanyl were distributed into three groups: (1) low-dose agmatine (10 mg/kg) throughout self-administration; (2) high-dose agmatine (30 mg/kg) throughout self-administration; and (3) high-dose agmatine after significant escalation (Day 18) of drug intake had occurred. Animals in a fourth group were pretreated with a high dose of agmatine throughout 30 days of cocaine self-administration. Both doses of agmatine, when given throughout self-administration, significantly decreased the escalation of responding that occurred for fentanyl but not cocaine. In the group that received agmatine after significant escalation had occurred, fentanyl-maintained responding was not significantly altered. These data indicate that agmatine attenuates the escalation of fentanyl self-administration if administered before the escalation begins and may mediate neuroadaptive events related to chronic opioid self-administration.

Agmatine↗
PubMed2003

Chronic access to a sucrose solution enhances the development of conditioned place preferences for fentanyl and amphetamine in male Long-Evans rats.

Consumption of palatable food and fluids alters the behavioral consequences of psychoactive drugs. To further investigate the effects of intake of palatable nutrients on the rewarding properties of these drugs, the effects of chronic intake of a sweet sucrose solution on the development of conditioned place preferences (CPP) to a mu-opioid agonist, fentanyl, and to a stimulant drug, amphetamine, were examined. Male Long-Evans rats consumed laboratory chow and water or chow, water, and a 32% sucrose solution. CPP testing was conducted in a three-chamber apparatus. In Experiment 1 (over four conditioning days), rats received saline, 0.004, or 0.016 mg/kg sc fentanyl citrate before being placed on the nonpreferred side of the apparatus and saline (subcutaneously) before being placed on the preferred side during a separate session on the same day. When given access to all three chambers, rats injected with 0.016 mg/kg fentanyl spent significantly more time on the drug-paired side than rats injected with saline. Furthermore, sucrose-fed rats displayed a significantly greater CPP than chow-fed rats. After conditioning, rats were tested for fentanyl-induced antinociception using the tail-flick test. Using a cumulative dose procedure, fentanyl (0.003, 0.010, 0.030, and 0.100 mg/kg sc) led to dose-dependent increases in tail-flick latencies. Rats fed with sucrose displayed significantly greater responses to fentanyl than those in the chow group. In Experiment 2, rats spent significantly more time on the drug-paired side of the CPP apparatus following injections of 0.33 or 1.0 mg/kg amphetamine than after saline injections. Additionally, following injection of 0.33 mg/kg amphetamine, sucrose-fed rats spent significantly more time on the drug-paired side of the chamber than chow-fed rats.

Amphetamine↗
PubMed2000

Evaluation of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) gels as a release vehicle for percutaneous fentanyl.

The primary objective of this study was to investigate the feasibility of PEO-PPO-PEO copolymer gel as a release vehicle for percutaneous administration of fentanyl in vitro and in vivo. A cellulose membrane and nude mouse skin with series concentrations of PEO-PPO-PEO block copolymers were used to examine the sustained-release pattern and permeation of fentanyl. The in vivo percutaneous absorption was examined using rabbits to evaluate the preliminary pharmacokinetics of fentanyl with 46% PEO-PPO-PEO copolymer formulation patches. The micelle formation ability of this block copolymer and the penetration ability of PEO-PPO-PEO copolymer over time were also studied by pyrene fluorescence probe methods and the dynamic light scattering test. At a concentration of 46% at 37 degrees C, PEO-PPO-PEO copolymers formed a gel and showed a pseudo-zero-order sustained-release profile. With increasing concentration of copolymer in the cellulose membrane transport, the apparent release flux of fentanyl (200 microgram/ml) decreased to 1. 09+/-0.19 microgram cm(-2) h(-1). Assessment of the effect of the copolymer on nude mouse skin also showed a decrease in the apparent permeability coefficient [(P(H(2)O))=2.24+/-0.47x10(-6) cm s(-1) vs. (P(46% block copolymer))=0.93+/-0.23x10(-7) cm s(-1)]. The preliminary pharmacokinetics of the fentanyl patch was shown to be in steady state within 24 h, and this was maintained for at least 72 h with an elimination half-life (t(1/2)) of 10.5+/-3.4 h. A fluorescence experiment showed polymeric micelle formation of PEO-PPO-PEO copolymers at 0.1% (w/w) within 50 nm micelle size and the PEO-PPO-PEO copolymers were able to penetrate nude mouse skin within 24 h. Thus, it appears that fentanyl preparations based on PEO-PPO-PEO copolymer gel might be practical for percutaneous delivery.

Administration, Cutaneous↗
PubMed1989

The safety of fentanyl use in the emergency department.

Fentanyl citrate is a synthetic narcotic 1,000 times as potent as meperidine. It produces minimal hemodynamic effects and is characterized by a rapid onset of sedation and analgesia, a relatively short duration of action (approximately 30 to 40 minutes), and rapid reversal with opiate antagonists. These properties make fentanyl an ideal drug for emergency department use. The safety of fentanyl use in an adult ED population has not previously been studied. We retrospectively reviewed the charts of 841 patients who received fentanyl at the University of Cincinnati Center for Emergency Care between January 1985 and June 1988. The study population included 497 (59%) men and 344 (41%) women, with an average age of 33 years. The average dose of fentanyl was 180 micrograms (range, 25 to 1,400 micrograms). Six patients (1%) experienced mild side effects including nausea (one), emesis (two), urticaria (one), and pruritus (two). Nine patients (1%) developed more serious complications including six cases (0.7%) of respiratory depression and three cases (0.4%) of hypotension. Two of 183 patients (1%) who received midazolam and two of nine patients (22%) who received haloperidol developed respiratory depression. Four of the six patients with respiratory depression and two of the three patients with hypotension were intoxicated. All of the complications were transient, and none resulted in hospitalization. We conclude that fentanyl is a safe drug for use in the ED. To maximize safety, we recommend careful dosing and titration, close patient monitoring, and the availability of naloxone hydrochloride and resuscitation equipment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1999

Fentanyl increases dopamine release in rat nucleus accumbens: involvement of mesolimbic mu- and delta-2-opioid receptors.

The effects of the mu-receptor agonist fentanyl on extracellular levels of dopamine in rat nucleus accumbens were studied in awake animals by in vivo brain microdialysis. Fentanyl dose-dependently increased the levels of dopamine when given intravenously (microg/kg) or via a microdialysis probe placed into the ventral tegmental area or the nucleus accumbens (nmol). The effect of fentanyl given into the nucleus accumbens was blocked by systemic administration of the non-selective opioid receptor antagonist naloxone and by accumbens administration of D-Phe-Cys-Tyr-D-Trp-Om-Thr-Phe-Thr-NH2 (nmol), a mu-opioid receptor antagonist, and naltrindole (nmol), a non-selective delta-opioid receptor antagonist, in a dose-dependent manner. The delta2-opioid receptor antagonist, naltriben (nmol), also blocked the effects of fentanyl, whereas the delta1-opioid receptor antagonist, (E)-7-benzylidenenaltrexone (nmol), was ineffective. When marginally effective doses of D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH2 and naltriben were given simultaneously, the effect of fentanyl was nearly fully blocked; the pretreatment itself had no effect. Administration of the mu-opioid receptor agonist [D-Ala2, N-Me-Phe4,Gly5-ol]-enkephalin (nmol), the delta1-opioid receptor agonist [D-Pen2,5]-enkephalin (nmol) or the delta2-opioid receptor agonist [D-Ala2,Glu4]-deltorphin (nmol) into the nucleus accumbens enhanced the amount of accumbal dopamine. This study provides evidence that not only activation of delta1- and delta2-opioid receptors, but also activation of mu-opioid receptors in the nucleus accumbens increases the release of accumbal dopamine in freely moving rats. We suggest that the effect of intra-accumbens administration of fentanyl upon accumbal release of dopamine is either due to the simultaneous activation of mu-opioid receptors and delta2-opioid receptors or due to activation of mu-opioid receptors that interact with delta2-opioid receptors in a complex manner.

Analgesics, Opioid↗
PubMed2002

Preparation and characterization of fentanyl-loaded PLGA microspheres: in vitro release profiles.

We developed several kinds of fentanyl-loaded poly(L-lactide-co-glycolide) (PLGA) microspheres (FMS) for sustained release of fentanyl. FMS were prepared by an emulsion solvent-evaporation method. In this study, the influences of several preparation parameters, such as initial drug loading, polymer concentration, and solvent volume on the release patterns of fentanyl were investigated. Furthermore, it has been well noted that the detection of fentanyl is extremely difficult because its clinical dose level is very low, about 1-3 ng/ml, in cancer-patient treatment. Therefore, we also developed a rapid and sensitive determination method for fentanyl in systemic circulation by employing gas chromatography (GC) system. Fentanyl was slowly released from FMS over 15 days with a quasi-zero order property. From the results, our FMS may be good formulations to deliver the analgesics and suitable for the treatment of severe pain over long periods.

Analgesics, Opioid↗
PubMed2000

Comparison of nonradioactive microtiter plate enzyme immunoassays for the sensitive detection of fentanyl.

Fentanyl is a very strong opioid with analgesic properties that are approximately 80 times stronger than those of morphine and therefore is used in major surgery and treatment of pain in tumor patients. Cases of fentanyl abuse by intravenous injection, inhalation, oral or nasal application have been reported especially in the USA. Therapeutic levels of fentanyl are as low as 1 ng/ml of serum and therefore a screening test must have a detection limit below that concentration. Recently three non-radioactive enzyme immunoassays (EIAs) have become commercially available from COZART, STC and DIAGNOSTIX, all of them supplied by MAHSAN Diagnostika for evaluation with serum samples from forensic and clinical cases. A calibration curve is obtained with samples that contain 0, 0.1, 0.5, 1 and 5 ng fentanyl per ml of negative serum. The calibration curve of COZART is especially in the low range, steeper than those of STC and DIAGNOSTIX. The cut-off for all these EIAs, however, can be set at 0.5 ng/ml. After the administration of therapeutic doses, fentanyl concentrations were between 3 and more than 5 ng/ml as determined with the EIAs. The presence of the typical drugs of abuse, e.g. heroin, methadone, cocaine, cannabinoids and amphetamines including the derivatives of methylenedioxyamphetamine, don't generate false-positive results. No cross-reactivity was also observed at toxic levels of benzodiazepines and paracetamol and therapeutic levels of barbiturates, phenothiazines, antidepressants and analgesics. The EIAs tested so far appear to be suitable for the detection of fentanyl at therapeutic levels. False-positive results or cross-reactivity towards other compounds have not been observed.

Analgesics, Opioid↗