Showing papers on "Buprenorphine published in 2000"

A Comparison of Levomethadyl Acetate, Buprenorphine, and Methadone for Opioid Dependence

Abstract: Background Opioid dependence is a chronic, relapsing disorder with important public health implications. Methods In a 17-week randomized study of 220 patients, we compared levomethadyl acetate (75 to 115 mg), buprenorphine (16 to 32 mg), and high-dose (60 to 100 mg) and low-dose (20 mg) methadone as treatments for opioid dependence. Levomethadyl acetate and buprenorphine were administered three times a week. Methadone was administered daily. Doses were individualized except in the group assigned to low-dose methadone. Patients with poor responses to treatment were switched to methadone. Results There were 55 patients in each group; 51 percent completed the trial. The mean (±SE) number of days that a patient remained in the study was significantly higher for those receiving levomethadyl acetate (89±6), buprenorphine (96±4), and high-dose methadone (105±4) than for those receiving low-dose methadone (70±4, P<0.001). Continued participation in the study was also significantly more frequent among patients rec...

Adherence to HAART in French HIV-infected injecting drug users : The contribution of buprenorphine drug maintenance treatment

Abstract: Objectives To assess adherence to highly active antiretroviral therapies (HAART) in a cohort of French patients infected by HIV through injection drug use (IDU), and the impact on adherence of buprenorphine ambulatory drug maintenance treatment (DMT) which has been widely introduced since 1996. Design Adherence assessment at first visit after initiation of HAART in the MANIF2000 cohort study. Methods Patient's face-to-face and self-administered questionnaires. Univariate and logistic regression adjusted odds ratios (OR) to compare characteristics of non-adherent versus adherent patients. Results Of the 164 patients, 34.8% took less than 80% of the prescribed HAART doses during the previous week. Decrease in viral load titres after initiation of HAART was significantly lower among non-adherent patients. After adjustment by logistic regression, non-adherence was associated with younger age, alcohol consumption, frequency of negative life-events during the prior 6 months and active drug use. However, IDU in buprenorphine DMT reached higher levels of adherence (78.1%) than ex-IDU (65.5%), although this difference did not reach statistical significance. Conclusion Prescription of buprenorphine DMT may increase adherence to HAART among HIV-infected opiate-dependent patients. Reducing the negative impact of stressful life-events through psychosocial interventions should be considered, even for those who have stopped using drugs.

Clinical Pharmacokinetics of Transdermal Opioids Focus on Transdermal Fentanyl

Abstract: Transdermal delivery allows continuous systemic application of opioids through the intact skin. This review analyses the pharmacokinetic properties of transdermal opioid administration in the context of clinical experience, with a focus on fentanyl. A transdermal therapeutic system (TTS) for fentanyl has been developed. The amount of fentanyl released is proportional to the surface area of the TTS, which is available in different sizes. After the first application of a TTS, a fentanyl depot concentrates in the upper skin layers and it takes several hours until clinical effects are observed. The time from application to minimal effective and maximum serum concentrations is 1.2 to 40 hours and 12 to 48 hours, respectively. Steady state is reached on the third day, and can be maintained as long as patches are renewed. Within each 72-hour period, serum concentrations decrease gradually over the second and third days. When a TTS is removed, fentanyl continues to be absorbed into the systemic circulation from the cutaneous depot. The terminal half-life for TTS fentanyl is approximately 13 to 25 hours. The interindividual variability of serum concentrations, partly caused by different clearance rates, is markedly larger than the intraindividual variability. The effectiveness of TTS fentanyl was first demonstrated in acute postoperative pain. However, the slow pharmacokinetics and large variability of TTS fentanyl, together with the relatively short duration of postoperative pain, precluded adequate dose finding and led to inadequate pain relief or, especially, a high incidence of respiratory depression; such use is now contraindicated. Conversely, in cancer pain, TTS fentanyl offers an interesting alternative to oral morphine, and its effectiveness and tolerability in this indication has been demonstrated by a number of trials. Its usefulness in chronic pain of nonmalignant origin remains to be confirmed in controlled trials. In general, TTS fentanyl produces the same adverse effects as other opioids, mainly sedation, nausea, vomiting and constipation. In comparison with oral morphine, TTS fentanyl causes fewer gastrointestinal adverse events. The risk of hypoventilation is comparatively low in cancer patients. Sufentanil and buprenorphine may also be suitable for transdermal delivery, but clinical results are not yet available. Transdermal morphine is only useful if applied to de-epithelialised skin. However, iontophoresis may allow transdermal administration of opioids, including morphine, with a rapid achievement of steady state concentrations and the ability to adjust delivery rates. This would be beneficial for acute and/or breakthrough pain, and initial clinical trials are in progress.

Treatment of opioid‐dependent pregnant women with buprenorphine

Abstract: Aims: To assess the maternal and fetal acceptability of buprenorphine and neonatal abstinence syndrome (NAS) in children born to buprenorphine-maintained mothers. Design and setting: Open-label, flexible dosing, inpatient induction with outpatient maintenance, conducted at the University of Vienna within the existing pregnancy and drug addiction program. Participants: Fifteen opioid-dependent pregnant women. Intervention. Sublingual buprenorphine tablets (1-10 mg/day). Measurements: Mothers: withdrawal symptoms (Wang Scale), nicotine dependence (Fagerstrom Scale: FTQ) and urinalysis. Neonates: birth outcome and NAS (Finnegan Scale). Findings: All subjects were opioid-, nicotine- and cannabis-dependent. Buprenorphine was well tolerated during induction (Wang Score \< = 4) and illicit opioid use was negligible (91% opioid-negative). All maternal, fetal and neonatal safety laboratory measures were within normal limits or not of clinical significance. Mean birth outcome measures including gestational age at delivery (39.6 ± 1.5 weeks), Apgar scores (1 min = 8.9; 5 min = 9.9; and 10 min = 10), birth weight (3049 ± 346 g), length (49.8 ± 1.9 cm) and head circumference (34.1 ± 1.8 cm) were within normal limits. The NAS was absent, mild (without treatment) and moderate (with treatment) in eight, four and three neonates, respectively. The mean duration of NAS was 1.1 days. Conclusions: Buprenorphine appears to be well accepted by mother and fetus, and associated with a low incidence of NAS. Further investigation of buprenorphine as a maintenance agent for opioid-dependent pregnant women is needed.

Sex-related differences in the antinociceptive effects of opioids: importance of rat genotype, nociceptive stimulus intensity, and efficacy at the µ opioid receptor

Abstract: Rationale: Recent studies indicate that morphine is more potent as an antinociceptive agent in male than female rodents and monkeys. Objectives: To evaluate the influence of sex, nociceptive stimulus intensity and an opioid's relative efficacy on opioid-induced antinociception in rat strains (F344 and Lewis) that display differential sensitivity to morphine antinociception. Methods: Antinociceptive testing was conducted using a rat warm-water (50–56°C) tail-withdrawal procedure. Dose–response and time-course determinations were performed with various opioids. Results: Across the nociceptive stimulus intensities tested, the high-efficacy µ opioids morphine, etorphine, and levorphanol were equally effective in males and females, but on average 2.5-fold more potent in males. At moderate stimulus intensities, the low-efficacy µ opioid buprenorphine was approximately 0.4-fold more potent in males, and at higher stimulus intensities more potent and effective (greater maximal effect) in males. At low stimulus intensities, the low-efficacy µ opioid dezocine and the µ/κ opioid butorphanol were greater than 8.9-fold more potent in males, and at moderate stimulus intensities were more potent and effective in males. At a low stimulus intensity, the µ/κ opioid nalbuphine was more potent and effective in males. At stimulus intensities in which buprenorphine, dezocine, butorphanol, and nalbuphine produced maximal effects in males but not females, these opioids antagonized the effects of morphine in females. Genotype-related differences were noted as opioids were generally more potent in F344 than Lewis males, whereas no consistent differences were observed between F344 and Lewis females. Conclusions: That sex differences in the potency and effectiveness of opioids increased with decreases in the opioid's relative efficacy and with increases in the nociceptive stimulus intensity suggests that the relative efficacy of µ opioids as antinociceptive agents is greater in male than female rats.

The magnitude and duration of the analgesic effect of morphine, butorphanol, and buprenorphine in rats and mice.

Abstract: This study was designed to determine the magnitude and duration of the analgesic effect of three commonly used opioids: buprenorphine (0.5 mg/kg for rats; 2.0 mg/kg for mice), butorphanol (2.0 mg/kg for rats; 5.0 mg/kg for mice), and morphine (10 mg/kg for rats and mice). We used two standard tests, the hot plate and tail flick assays, to measure opioid analgesia in 62 male, 200 to 300 g Sprague-Dawley rats and 61 male, 25 to 35 g ICR mice. We obtained five baseline measurements then administered the drugs subcutaneously. Morphine gave the highest analgesic effect and was intermediate in duration (2 to 3 h in rats and mice) of analgesia. Butorphanol provided the lowest level of and shortest (1 to 2 h in rats and mice) analgesia. Buprenorphine had an intermediate analgesic effect and the longest duration (6 to 8 h in rats and 3 to 5 h in mice). In light of our results, we recommend the use of morphine (with frequent redosing) for severe pain, butorphanol for mild pain of short duration, and buprenorphine for mild to moderate pain of increased duration. The dosing intervals suggested by our study are 2 to 3 h for morphine in both rats and mice, 1 to 2 h for butorphanol in both rats and mice; and 6 to 8 h in rats and 3 to 5 h in mice for buprenorphine.

Treatment of heroin-dependent poly-drug abusers with contingency management and buprenorphine maintenance.

Abstract: This study targeted poly-drug (cocaine plus heroin) abstinence among buprenorphine-maintained participants with a 12-week voucher-based reinforcement therapy (VBRT) phase versus a yoked control condition Baseline levels of cocaine and heroin use were significant predictors of treatment outcome, regardless of treatment assignment Overall, there were no significant group differences on treatment outcome However, among the subsample that produced one or more poly-drug-free urine results, VBRT participants had significantly increased cocaine-but not heroin and poly-drug-abstinence, although all results were in the predicted direction Results suggest that for those who achieve poly-drug abstinence, VBRT may enhance treatment outcome However, improved interventions, perhaps targeting single-drug abstinence, increasing reinforcement magnitude, or both, may be necessary to promote initial poly-drug abstinence in this population

Effects of buprenorphine versus buprenorphine/naloxone tablets in non- dependent opioid abusers

Abstract: Rationale: Buprenorphine is an opioid agonist-antagonist under development in the United States as a sublingual medication for treatment of opioid dependence. Buprenorphine may be abused; therefore, tablets combining buprenorphine with naloxone have been developed with the intent of reducing the abuse risk in people physically dependent upon opioids. The characteristics and abuse potential of buprenorphine and buprenorphine/naloxone tablets in non-dependent opioid abusers have not been determined. Non-parenteral abuse of opioids such as buprenorphine may be more likely in people who have less severe substance abuse disorders (e.g., are not physically dependent upon opioids). Objectives: To assess the abuse potential of sublingual buprenorphine and buprenorphine/naloxone tablets in non-dependent opioid abusers. Methods: Subjects (n=7) were tested with sublingual buprenorphine (4, 8, 16 mg), sublingual buprenorphine/naloxone (1/0.25, 2/0.5, 4/1, 8/2, 16/4 mg), as well as intramuscular hydromorphone as an opioid agonist control (2, 4 mg) and placebo in laboratory sessions conducted twice per week. Dosing was double-blind and double-dummy. Results: The higher doses of both buprenorphine and buprenorphine/naloxone produced similar opioid agonist-like effects. The onset of these effects was slowed, consistent with the sublingual route of administration, and the magnitude of effects was moderate. There was no evidence to suggest the addition of naloxone attenuated buprenorphine’s opioid agonist effects in this population when buprenorphine was delivered by the sublingual route. Conclusions: These results suggest that sublingual buprenorphine and buprenorphine/naloxone may both be abused by opioid users who are not physically dependent upon opioids.

Buprenorphine or procaine for pain relief in acute pancreatitis. A prospective randomized study.

Abstract: Background: To assess the analgesic efficacy and side effects of buprenorphine and procaine in patients with acute pancreatitis. Methods: Forty patients (average age, 50 years; 23 male) with acute ...

Buprenorphine and naloxone for heroin dependence.

Abstract: The pharmacology of buprenorphine is unique because of its partial agonist profile at the mu-opioid receptor (ie, high affinity, low intrinsic activity and slow dissociation). This unique profile results in greater safety, less physical dependence, and greater flexibility in dose scheduling. Buprenorphine has been investigated in combination with the opioid antagonist, naloxone, with the goal of decreasing abuse, misuse, and diversion. When combined with naloxone in a sublingual tablet, buprenorphine has been shown to be effective 1) in retaining patients in treatment, 2) in reducing opioid use and craving, and 3) when dosed less-than-daily. The pharmacologic effects of buprenorphine are not altered by the addition of naloxone when administered to the population in an appropriate combination ratio. However, if taken intravenously by individuals dependent on short- or long-acting opioids a precipitated withdrawal syndrome is observed, which should reduce its abuse potential. This review discusses the rationale for development and evidence supporting the use of a buprenorphine/naloxone combination product. The buprenorphine/naloxone combination product should be considered for use in primary care office-based settings as a safe and effective treatment that is likely to increase the availability of agonist treatment for opioid dependence.

Elevated liver enzyme levels in opioid-dependent patients with hepatitis treated with buprenorphine.

Abstract: The purpose of this study was to assess changes in liver enzyme levels among opioid-dependent patients treated with buprenorphine. Liver enzyme levels were evaluated among 120 individuals before treatment and following a minimum of 40 days of buprenorphine treatment (2, 4, or 8 mg/70 kg/day). Among patients with a history of hepatitis, AST and ALT levels significantly increased (p < .05) with buprenorphine treatment. The odds of observing an increase in AST were determined to be dependent upon buprenorphine dose (p < .05; odds ratio = 1.23 per 1 mg increase in dose). These results suggest that liver enzyme levels should be monitored carefully when patients with hepatitis are treated with buprenorphine.

Transdermal fentanyl compared with parenteral buprenorphine in post-surgical pain in swine: a case study

Abstract: Summary The use of pigs as research animals in survival surgery has increased greatly in the last 15 years. Personnel conducting pig research have been hampered by a lack of proven longacting analgesics for treatment of surgical pain of longer duration, and bya lack of reliable non-subjective parameters for the assessment of pain relief. The efficacy of the mixed opioid agonist-antagonist buprenorphine hydrochloride 0.10 mg/kg pm (n = 2) in the treatment of post-thoracotomy pain was compared with that of a trans dermal therapeutic system (TTSI delivering 25 {tg/h (n = 3) or SOflg/h (n = 2) of the mu opioid agonist fentanyl hydrochloride. Food consumption, pain score, activity level and rate of movement were assessed under four conditions: normal pre-operative control (24 h), pre-operative with analgesic alone 124hI and post-operative days I, 2, 3 (72 h). Serum concentration-time curves for fentanyl in clinical cases revealed that female Yorkshire cross pigs weighing 26.2±2.1 kg achieved serum values in the recognized human therapeutic range when treated with TTS fentanyl at SOflg/h and experienced adequate pain control. Pigs treated with 25 flg/h TTS fentanyl had serum levels below the human analgesic range, experienced less adequate analgesia, and required supplemental analgesia in some cases. Based on existing pharmacokinetic data for fentanyl in pigs, the rate of uptake of TIS fentanyl when attached on inter-scapular skin was lower than predicted. Clinical pain scores and time intervals between each major postural change were not affected by analgesics in the absence of pain, but increased in all groups after surgery regardless of treatment. Food consumption was unaffected by analgesic treatment alone but decreased in all groups after surgery regardless of treatment. Analgesic effects on postoperative activity level were variable. TTS fentanyl at appropriate doses is a cost effective means of delivering basal analgesia following major surgery in pigs.

Buprenorphine or Procaine for Pain Relief in Acute Pancreatitis

Abstract: BACKGROUND To assess the analgesic efficacy and side effects of buprenorphine and procaine in patients with acute pancreatitis. METHODS Forty patients (average age, 50 years; 23 male) with acute pancreatitis or an acute bout of a chronic pancreatitis were prospectively randomized to receive buprenorphine or procaine for pain relief. Both analgesics were administered as constant intravenous (i.v.) infusions and additional analgesics were given on demand. Pain scores were assessed on a visual analogue scale. Close clinical control and laboratory checks were performed during the three-day study period. RESULTS Patients receiving buprenorphine were significantly less likely to demand additional analgesics (1 versus 14 patients; P < 0.0001). The pain scores for patients in the buprenorphine group were significantly lower over the treatment period in comparison to procaine (P < 0.05). The reduction of pain score was significantly greater during the initial two treatment days using buprenorphine (day 1: 55 versus 25, P < 0.0001; day 2: 62 versus 40, P = 0.005). Side effects were comparable for both groups with the exception of a slightly higher sedation rate under buprenorphine. CONCLUSIONS Constant i.v. application of buprenorphine is more effective than the recommended procaine for pain relief in acute pancreatitis.

Toxicity and/or insufficient analgesia by opioid therapy: risk factors and the impact of changing the opioid. A retrospective analysis of 273 patients observed at a single center

Abstract: The charts of 273 cancer patients were retrospectively analyzed in order (1) to evaluate the frequency of opioid change (OCH) when adjuvants (antiemetics/laxatives) were administered on a regular basis and co-analgesic medication as indicated by the specific type of pain, (2) to define risk factors for the request of OCH, and (3) to reveal settings in which OCH may not be recommended as a first-line therapeutic intervention. Opioids used included morphine, fentanyl, l-methadone, and buprenorphine. Out of 273 patients, 103 changed opioids at least once, with a success rate of 65%. The indications for the OCH were insufficient analgesia in 43%, intolerable side effects in 20%, both in 15%, and other reasons in 22% of patients. The frequency of OCH was not influenced by the routine use of adjuvants or co-analgesics except corticosteroids, which raises queries about the concept of an opioid-sparing effect of co-analgesics. The occurrence of intolerable side effects is thought not to be dose dependent so much as to reflect differences in the individual tolerability of a distinct opioid for whatever reason (genetically fixed or individually acquired pharmacodynamic or kinetic properties). Moreover, there was strong evidence for the existence of an unpredictable and incomplete cross-tolerance between opioids, which meant careful titration of the new opioid was required after OCH. The overall frequency of OCH was similar to that observed in previous studies in spite of the documented addition of adjuvants and co-analgesics. This retrospective study supports the notion that opioid rotation must be retained as an essential therapeutic option even with optimized adjuvant and co-analgesic regimens.

Postoperative pain control following remifentanil-based anaesthesia for major abdominal surgery.

Abstract: Eighty patients undergoing major abdominal surgery using remifentanil-based anaesthesia were randomly allocated in a double-blind manner to receive an intravenous bolus of fentanyl, buprenorphine, morphine or piritramide 20 min before the end of surgery. A reduced dose was administered postoperatively when patients reported moderate pain. Subsequent analgesia was provided by patient-controlled analgesia (PCA). The mean time from the end of anaesthesia to spontaneous respiration was 9 +/- 5 min. At first pain assessment, 63% of patients reported no or mild pain; 80% of patients required the second opioid bolus, those receiving piritramide needed the bolus significantly later than patients receiving buprenorphine or fentanyl. First PCA requirement also occurred significantly later in the piritramide group. This technique provided effective postoperative pain relief and transition to routine PCA and did not compromise recovery.

Effects of Agonist-Antagonist Opioids in Humans Trained in a Hydromorphone/Not Hydromorphone Discrimination

Abstract: The purpose of this study was to examine the discrimination of agonist-antagonist opioids in humans trained in a two-choice hydromorphone/not hydromorphone discrimination. Eight adult male volunteers with histories of opioid abuse who were not currently physically dependent were trained to discriminate the mu receptor agonist hydromorphone (3 mg/70 kg, i.m.) (“Drug A”) from a “Not Drug A” training condition (saline placebo). Volunteers received financial reinforcement for correct responses. After training, generalization dose-effect curves for hydromorphone, butorphanol, pentazocine, nalbuphine, and buprenorphine were determined. Other subjective, behavioral, and physiological measures were concurrently collected in all sessions. In generalization testing hydromorphone and buprenorphine produced dose-related increases in hydromorphone-appropriate responses. Pentazocine produced an inverted U-shaped dose-response curve with complete substitution at 32 mg/70 kg but not at 64 mg/70 kg. Butorphanol and nalbuphine did not completely substitute for hydromorphone at any dose tested. These results differ from an earlier two-choice, Drug A versus Drug B (hydromorphone/saline) discrimination study. After Drug/Not Drug instructions the behavioral discriminations of agonist-antagonist opioids were more consistent with their putative agonist activities at the mu opioid receptor and with their subjective effects profiles than was the case after Drug A versus Drug B instructions. These results suggest that instructions are an important factor in the outcome of human drug discrimination studies.