Showing papers on "Buprenorphine published in 1999"

Buprenorphine versus methadone maintenance for the treatment of opioid dependence.

Abstract: Aims. To evaluate the effectiveness of buprenorphine compared with methadone maintenance therapy in opiate addicts over a treatment period of 24 weeks. Design. Subjects were randomized to receive either buprenorphine or methadone in an open, comparative study. Setting. Subjects were recruited and treated at the drug addiction outpatient clinic at the University of Vienna. Participants. Sixty subjects (19 females and 41 males) who met DSM-IV criteria for opioid dependence and were seeking treatment. Intervention. Subjects received either sublingual buprenorphine (2-mg or 8-mg tablets; maximum daily dose 8 mg) or oral methadone (racemic D2 /1 L-methadone; maximum daily dose 80 mg). A stable dose was maintained following the 6-day induction phase. Measurement. Assessment of treatment retention and illicit substance use (opiates, cocaine and benzodiazepines) was made by urinalysis. Findings. The retention rate was signi® cantly better in the methadone maintained group (p, 0.05) but subjects completing the study in the buprenorphine group had signi® cantly lower rates of illicit opiate consumption (p5 0.04). Conclusion. The results support the superiority of methadone with respect to retention rate. However, they also con® rm previous reports of buprenorphine use as an alternative in maintenance therapy for opiate addiction, suggesting that a speci® c subgroup may be bene® ting from buprenorphine. This is the ® rst comparative trial to use sublingual buprenorphine tablets: previously published comparison studies refer to 30% solutions of buprenorphine in alcohol.

Inducing placebo respiratory depressant responses in humans via opioid receptors.

Abstract: Several lines of evidence indicate that placebos produce analgesia through the activation of endogenous opioid systems. Recently, we showed that placebos may also produce respiratory depressant responses, a typical side-effect of narcotics, when a subject had a prior experience of respiratory depression in the course of narcotic treatment. In the present study, we report that the placebo respiratory depression can be induced after repeated administrations of the partial opioid agonist buprenorphine. The placebo respiratory depressant effect that resulted from the buprenorphine conditioning was completely blocked by a dose of 10 mg of naloxone, indicating that it was mediated by endogenous opioids. These findings show that placebos act, via the activation of opioid receptors, not only on pain mechanisms but on the respiratory centres as well, thus mimicking a typical side-effect of narcotics. In addition, the experimental procedure we used did not produce any expectation of respiratory depression and, similarly, the subjects did not notice any sign of respiratory discomfort. Thus, the placebo respiratory depression elicited in the present study cannot be explained on the basis of cognitive or motivational mechanisms. Rather, it appears to be a sequence effect due to learning, thus suggesting a conditioning mechanism mediated by endogenous opioids.

Buprenorphine and naloxone combinations : the effects of three dose ratios in morphine-stabilized, opiate-dependent volunteers

Abstract: Sublingual buprenorphine is a promising new treatment for opiate dependence, but its opioid agonist effects pose a risk for parenteral abuse. A formulation combining buprenorphine with the opiate antagonist naloxone could discourage such abuse. The effects of three intravenous (IV) buprenorphine and naloxone combinations on agonist effects and withdrawal signs and symptoms were examined in 12 opiate-dependent subjects. Following stabilization on a daily dose of 60 mg morphine intramuscularly, subjects were challenged with IV doses of buprenorphine alone (2 mg) or in combination with naloxone in ratios of 2:1, 4:1, and 8:1 (1, 0.5, or 0.25 mg naloxone), morphine alone (15 mg) or placebo. Buprenorphine alone did not precipitate withdrawal and had agonist effects similar to morphine. A naloxone dose-dependent increase in opiate withdrawal signs and symptoms and a decrease in opioid agonist effects occurred after all drug combinations. Buprenorphine with naloxone in ratios of 2:1 and 4:1 produced moderate to high increases in global opiate withdrawal, bad drug effect, and sickness. These dose ratios also decreased the pleasurable effects and estimated street value of buprenorphine, thereby suggesting a low abuse liability. The dose ratio of 8:1 produced only mild withdrawal symptoms. Dose combinations at 2:1 and 4:1 ratios may be useful in treating opiate dependence.

Onset, magnitude and duration of opioid blockade produced by buprenorphine and naltrexone in humans.

Abstract: Rationale: One therapeutic benefit of mu opioid agonist or antagonist maintenance is the resultant attenuation of the effects of illicit opioids. It is important to characterize the development and duration of opioid blockade produced by buprenorphine, a novel opioid dependence pharmacotherapy. Objective: This study characterized the ability of buprenorphine to attenuate opioid effects during treatment initiation and discontinuation compared to naltrexone and placebo. Methods: Opioid-experienced volunteers (n = 8) participated in this 10-week, inpatient, double-blind, within-subject, crossover study. Five randomized conditions [buprenorphine (2 and 8 mg, sublingually), naltrexone (25 and 100 mg, PO) and placebo] were each examined during a 2-week period; the test drug was given for 7 days followed by a 7-day placebo wash-out. Cumulative doses of hydromorphone (0, 2 and 4 mg, IM, 45 min apart) were administered thrice-weekly corresponding with treatment and wash-out days 1, 3, and 5; behavioral, physiological and pharmacokinetic measures were collected. Results: Buprenorphine alone produced dose-related prototypic agonist effects during induction (i.e., positive mood, respiratory depression, miosis); tolerance developed only to the subjective effects. Buprenorphine 2 mg partially attenuated the effects of hydromorphone, while nearly complete attenuation was observed with 8 mg that lasted up to 72 h after discontinuation. Both naltrexone doses produced complete hydromorphone blockade after a single dose; blockade of the behavioral, but not physiological, effects persisted for 5 days after discontinuation of 100 mg. Conclusions: These data suggest that 2 mg buprenorphine is a sub-therapeutic maintenance dose, both buprenorphine 8 mg and naltrexone produce immediate and efficacious opioid blockade, and adequate protection against illicit opioids may be achieved with less-than-daily dosing.

Buprenorphine dosing every 1, 2, or 3 days in opioid-dependent patients.

Abstract: Rationale: Administration of double the maintenance dose of buprenorphine has been shown to permit every-other-day dosing. Whether longer periods between dosing can be achieved is unknown. Objectives: To examine whether triple the maintenance dose can be administered every 72 h without opioid withdrawal or intoxication. Methods: Sixteen opioid-dependent outpatients each received three conditions (1) the maintenance dose of buprenorphine every 24 h, (2) double the maintenance dose every 48 h, and (3) triple the maintenance dose every 72 h under double-blind placebo-controlled conditions. Each conditions was imposed in a random sequence for 21–22 days. Self report and observer measures were taken at 24-h intervals. Results: No significant differences were observed on measures of opioid agonist and withdrawal effects between the dosing conditions. However, averaging effects across conditions may obscure important within-condition effects. When conditions were analyzed by individual days within a condition, several significant effects were observed. For example, 24 h after administration of triple the maintenance dose, significant effects were observed in eight opioid agonist measures. Also, 72 h after administration of triple the maintenance dose, significant effects were observed on four measures of withdrawal. Neither adverse medical reactions nor excessive opioid intoxication were observed. Conclusions: These results suggest that buprenorphine may be administered safely every 72 h by tripling the maintenance dose, with only minimal withdrawal complaints. Importantly, this 72-h dosing may permit patients to attend clinic thrice weekly without the use of take-home doses.

Clinical experience using intrathecal (IT) bupivacaine infusion in three patients with complex regional pain syndrome type I (CRPS‐I)

Abstract: Background and aim: To date, there is no reliable method for treating the severe pain and for modifying the natural evolution of CRPS-I. Therefore, we explored the effect of long-term IT bupivacaine infusion (with or without buprenorphine) on this syndrome. Patients and methods: (a) Patients: two women and one man, 25, 31 and 42 years old, with CRPS-I of the lower (n=2) or upper (n=1) extremity lasting for 4 and 5 months, and 14 years. (b) Interventions: insertion of externalized IT catheters; IT infusion of buprenorphine 0.015 mg/ml and bupivacaine 4.75 mg/ml (n=1), or only bupivacaine 5 mg/ml (n=2) from external electronic pumps. Results: The IT treatment lasted for 172, 282 and 668 days. The mean/maximal daily doses of the IT bupivacaine were 39/66, 55/80 and 69/125 mg, respectively. The pain intensity decreased from VASmean=7±1 to VASmean=2±2. None of the patients had regression of allodynia, edema, and trophic disturbances in the affected extremities. In 2 patients, the IT treatment did not prevent spread of the disease to the opposite extremity or the occurrence of phantom pain and stump allodynia after amputation. The IT catheters were withdrawn as being no longer needed: in 2 patients 56 and 458 days after amputation of the involved extremity, and in another one before replacement of the IT bupivacaine infusion with epidural dorsal column stimulation (EDCS). After termination of the IT treatment, the patients were observed for 1437, 1575, and 2689 days (until September 1, 1998). At that date, all the patients were alive, and still affected by their CRPS-I, either in the amputation stump (n=2), and/or in the opposite or remote extremities (n=2); further, two were unemployed and one worked for 75% of the time. One of them was taking up to 1500 mg of slow-release morphine to cope with pain. Conclusion: The IT pain treatment with bupivacaine (with or without buprenorphine) alleviated the “refractory” pain, but affected neither the associated symptoms and signs of the CRPS-I, nor its natural evolution. Thus, the IT treatment cannot be recommended in preference to other pain treatment regimens for CRPS-I.

Use of oral buprenorphine ('buprenorphine jello') for postoperative analgesia in rats - A clinical trial

Abstract: Buprenorphine (0.1, 0.2, 0.3 or 0.4 mg/kg) in a flavoured gelatin base was administered preoperatively to rats undergoing a flank laparotomy. A control group of animals underwent surgery and received only flavoured gelatin. Body weight loss was significantly greater in the group which received no analgesia than in any of the analgesic-treated groups (P 0.05). Between-group comparisons did not show any significant difference between the different dose rates of analgesia used on either the change in body weight or the reduction in food or water consumption. The results of this study support the use of buprenorphine jelly for post-surgical analgesia in rats. This route of delivery is easy to use, and causes a minimum of stress to the rats.

Access to narcotic addiction treatment and medical care: prospects for the expansion of methadone maintenance treatment.

Abstract: Methadone maintenance treatment (MMT) for opioid addiction is safe and effective but underutilized because of inaccessibility, under-financing and the stigma generally attached to maintenance therapies. In addition, cumbersome regulation of methadone prescription and treatment impedes the delivery of care and retards expansion of methadone maintenance into office practice settings. Exaggeration of the problem of methadone diversion further hinders development of MMT. Despite obstacles, methadone maintenance has been successfully expanded and extended into primary care settings abroad. Initial trials in the U.S. have shown that methadone maintenance in physician office-based settings yields positive results with some advantages over care in large methadone clinics. Alternatives to methadone, such as buprenorphine, are also being explored in primary care settings. With implementation of the NIH Consensus Statement on Effective Medical Treatment of Heroin Addiction, including training of primary care physicians, methadone maintenance treatment could reach many more patients, achieve higher success rates, and substantially reduce the deleterious effects of opioid addiction in the U.S.

Delta opioid antagonist effects of buprenorphine in rhesus monkeys.

Abstract: Buprenorphine is an opioid with high affinity for delta, mu and kappa opioid receptors. The delta receptor-mediated effects of buprenorphine in vivo have not been studied. Thus, the present study examined the delta receptor-mediated effects of buprenorphine in rhesus monkeys. In vitro assays of rece

Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone.

Abstract: Background Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and effective pharmacotherapies are needed for this combined dependence. Methods This 13-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of desipramine hydrochloride (0 or 150 mg/d) plus buprenorphine hydrochloride (12 mg/d) or methadone hydrochloride (65 mg/d) in 180 opioid-dependent cocaine abusers (124 men, 56 women). Supervised urine samples were obtained thrice weekly, and self-reported cocaine and heroin use was reported once weekly. Desipramine plasma levels were determined at weeks 4 and 10. Results In men, opioid abstinence was increased more rapidly over time when treated with methadone than with buprenorphine, whereas cocaine abstinence was increased more with buprenorphine than with methadone. In women, opioid abstinence was increased the least rapidly when treated with buprenorphine plus placebo, while cocaine abstinence was increased more rapidly over time when treated with methadone than with buprenorphine. Regardless of sex or opioid medication, desipramine increased opioid and cocaine abstinence more rapidly over time than placebo. Self-reported opioid use confirmed these findings. Desipramine plasma levels were higher in women than in men, particularly those on buprenorphine maintenance. Higher desipramine plasma levels were associated with greater opioid, but not cocaine, abstinence. Conclusions Desipramine may be a useful adjunctive medication in facilitating opioid and cocaine abstinence in opioid-maintained patients. The efficacy of opioid medications to treat opioid or cocaine dependence may differ by sex. These findings highlight the importance of including sex as a factor when examining treatment outcome in these types of trials.

Determination of buprenorphine and norbuprenorphine in urine and hair by gas chromatography-mass spectrometry.

Abstract: Buprenorphine, which is used in France as a substitution drug for opioid addiction, is widely abused, and several fatal cases have been reported. In order to confirm a recent intoxication or to establish retrospectively chronic abuse, a simple and reliable gas chromatographic-mass spectrometric method was developed and validated for quantitation of buprenorphine and its active metabolite norbuprenorphine in urine and hair. Two milliliters of urine or 50 mg of pulverized hair was submitted to a pretreatment (enzymatic hydrolysis for urine and decontamination with dichloromethane followed by incubation in 0.1 M HCI for hair). Buprenorphine-d4 was chosen as the internal standard. Selective solid-phase extraction with Bond Elut Certify columns provided recoveries higher than 85% for urine and 43% for hair. By using a mixture of MSTFA/TMSIM/TMCS (100:2:5), buprenorphine and norbuprenorphine produced stable silylated derivatives. The detection was carried out with a quadrupole mass detector working in El selected ion monitoring mode. Ions at m/z 450 and 468 were chosen for the quantitation of buprenorphine and norbuprenorphine, respectively (m/z 454 was used for the internal standard). Limits of quantitation were 0.25 and 0.20 ng/mL, respectively, for buprenorphine and norbuprenorphine in urine and 0.005 ng/mg for the two compounds in hair. Calibration curves were linear from 0 to 50 ng/mL in urine and from 0 to 0.4 ng/mg in hair. Between-day and within-day precisions were less than 8.4% in hair and 6.1% in urine for both molecules in all cases. This method was applied to urine and hair samples collected from patients in a withdrawal treatment program and demonstrated its good applicability in routine analysis and its benefit for clinicians. This technique, which requires instruments already available to many toxicology laboratories, offers an attractive alternative to more sophisticated techniques.

Evaluation of intraarticular opioid analgesia for the relief of articular pain in the domestic fowl.

Abstract: An experimental paradigm, based on the microcrystalline sodium urate-induced arthritis pain model, was used to investigate the potential peripheral analgesic properties of a variety of opioid agonists. The response criteria were changes in behavioral profiles and pain-related behaviors over 60 min commencing 1 h after intraarticular injection. The testing system was used to determine the potential optimum dose of intraarticular application of morphine sulphate (1-3 mg), fentanyl citrate (0.5-3 mg), and buprenorphine hydrochloride (0.05-1 mg). None of the opioid analgesics used had any effect on pain behavior, and it was concluded that opioids with a high affinity for the mu receptor when injected intraarticularly were unlikely to be of use in the treatment or diagnosis of inflammatory arthritic pain in the strain of domestic fowl chosen.

A comparison of four buprenorphine dosing regimens in the treatment of opioid dependence.

Abstract: Objectives This study compared 24-, 48-, 72-, and 96-hour buprenorphine dosing regimens in opioid-dependent outpatients. Methods Fourteen subjects received buprenorphine in a double-blind, placebo-controlled crossover trial. Daily sublingual maintenance doses were 4 mg/70 kg (n = 5) and 8 mg/70 kg (n = 9). After a stabilization period of maintenance administration, subjects received, in a random order, four dosing regimens for five repetitions of each regimen: a maintenance dose every 24 hours, a doubled maintenance dose every 48 hours, a tripled maintenance dose every 72 hours, and a quadrupled maintenance dose every 96 hours. In the latter three dosing regimens, subjects received placebo on the interposed day(s). Study participation was contingent on opioid abstinence and daily clinic attendance. Measures of subjective opioid agonist and withdrawal effects were assessed daily. Results Relative to standard maintenance dosing, none of the higher doses induced agonist effects. Changes in indices of subjective withdrawal effects were noted as the time since the last active dose increased during intermittent dosing regimens, but the magnitude of these effects was relatively low and was comparable to those found in other alternate-day dosing studies. Conclusions These results support the feasibility and safety of twice weekly buprenorphine dosing regimens. Clinical Pharmacology & Therapeutics (1999) 66, 306–314; doi:

A comparison of pre- and post-surgical administration of bupivacaine or buprenorphine following laparotomy in the rat.

Abstract: The effects of bupivacaine, a long-acting local anaesthetic, and buprenorphine, an opioid analgesic, administered either pre- or post-operatively, were investigated in a rat laparotomy model. Surgical anaesthesia was induced and maintained with halothane. The type of analgesic treatment was a significant factor in the reduction in body weight and food and water intake which occurred following surgery. The largest reductions were seen in the bupivacaine-treated groups and those animals which received no analgesics. The timing of administration of analgesics had no influence on the effect of bupivacaine administration. The group receiving buprenorphine before surgery showed less depression in food intake than the group receiving buprenorphine at the end of surgery. Animals which received buprenorphine showed less depression of activity than those receiving saline or bupivacaine.

The influence of pre-anaesthetic administration of buprenorphine on the anaesthetic effects of ketamine/medetomidine and pentobarbitone in rats and the consequences of repeated anaesthesia.

Abstract: Rats received pentobarbitone (60, 48 and 36 mg/kg i.p.) or ketamine/medetomidine (75/100, 60/80 and 45/60 mg/microg/kg i.p.) alone, or one hour following buprenorphine (0.5 mg/kg s.c.). Animals were anaesthetized once per week for 6 weeks with one of three anaesthetic doses according to a randomized block design. In the pentobarbitone group, animals which received buprenorphine had longer sleep times (236 +/- 22 cf. 204 +/- 21 min) and longer durations of surgical anaesthesia (83 +/- 14 cf. 27 +/- 8 min) (P<0.01), these effects being potentiated with increasing anaesthetic doses (P<0.01). A greater degree of respiratory depression was found in animals that received buprenorphine (P<0.01) although this was judged clinically acceptable in all cases. Unexpectedly high mortality and a high incidence of anaesthetic complications (nine of 16 animals) in the ketamine/medetomidine group made statistical analysis of these data impossible. We conclude that for pentobarbitone, pre-anaesthetic administration of buprenorphine reduces the dose of anaesthetic required to produce surgical anaesthesia, in addition to the presumed benefits of pre-emptive analgesia. In view of the high mortality encountered, we advise caution when considering pre-anaesthetic use of opioids in combination with ketamine/medetomidine in rats.

Intra-articular buprenorphine after knee arthroscopy: A randomised, prospective, double-blind study

Abstract: Background: Demonstration of peripheral opioid receptors in inflamed synovia supports the concept of peripheral opioid analgesia. The aim of this study was to evaluate the analgesic effect of intra-articular administration of buprenorphine after knee arthroscopy. Methods: In a double-blind randomised trial, 48 patients were assigned to four groups: group A patients received buprenorphine 100 μg i.a. and NaCl 0.9% i.m., group B patients received bupivacaine 0.25% 50 mg i.a. and NaCl 0.9% i.m., group C patients received NaCl 0.9% i.a. and buprenorphine 100 μg i.m., and group D patients received NaCl 0.9% i.a. and NaCl 0.9% i.m. Intensity of postoperative pain was evaluated by VAS at recovery (T 0 ) and 1, 3, 6, 12, 24 h after operation (T 1 , T 2 , T 3 , T 4 , T 5 ), at rest and during passive 10° knee flexion. Total analgesic requirements and side effects related to study drugs were recorded. Results: The VAS scores were significantly higher in groups C and D than in group A and B patients. The differences were significant at T 0 , T 1 , T 2 and T 3 . At T 1 , group C and D patients had greater analgesic requirement than groups A and B. No patients developed side effects. Conclusion: Intra-articular buprenorphine and i.a. bupivacaine, both produced equally good postoperative pain control and allowed a significant reduction of analgesic requirement after knee arthroscopy.

Assessment of Opioid Partial Agonist Activity with a Three-Choice Hydromorphone Dose-Discrimination Procedure

Abstract: The discriminative stimulus and subjective effects of opioid mixed agonist-antagonists were assessed in volunteer nondependent heroin users trained in a three-choice drug discrimination procedure to discriminate among the effects of i.m. administration of 2 ml of saline, 1 mg of hydromorphone, and 4 mg of hydromorphone (a morphine-like μ agonist). Other subjective, behavioral, and physiological measures were concurrently collected. The discrimination was readily learned by six of the eight subjects. After training, generalization curves were determined for the following i.m. drug conditions: hydromorphone (0.375–4.0 mg), pentazocine (7.5–60 mg), butorphanol (0.75–6 mg), nalbuphine (3–24 mg), and buprenorphine (0.075–0.6 mg). All five of the test drugs were discriminated significantly or showed trends toward being discriminated as hydromorphone 1 mg-like at one or more dose levels. Hydromorphone showed an inverted U-shaped dose-effect function on the hydromorphone 1 mg-like discrimination. Subjective effect measures produced clearer differentiation among the test drugs than did drug discrimination performance. The present results differ from those of a previous study that observed a close relationship between the results of the discrimination measure and subjective effect measures. The previous study used similar methods and test drugs but different training drugs (e.g., 3 mg of hydromorphone versus 6 mg of butorphanol versus saline). It appears that both the sensitivity of drug discrimination performance to between-drug differences and the relationship between discriminative and subjective effects depends upon the specific discrimination that is trained (e.g., two-choice or three-choice). The present high dose-low dose-saline discrimination procedure appears useful for assessing partial agonist activity. The present data are consistent with partial agonist activity for pentazocine, butorphanol, nalbuphine, and buprenorphine.

Hepatonephritis and massive ingestion of buprenorphine

Abstract: We present a case of a severe hepatitis associated with acute renal failure and anuria consequently to the ingestion of 112 mg of buprenorphine, 48 hours before. The normalisation of hepatic and renal functions is associated with discontinuation of buprenorphine administration and hemodialysis treatment. Buprenorphine seems to be directly responsible for this hepatonephritis as indicated by the high plasmatic levels of buprenorphine (224 ng/ml) and norbuprenorphine (30 ng/ml) never described until now. Buprenorphine toxicity could be due to the inappropriate ingestion mode (oral instead of sublingual) and could be increased by previous acetaminophen intake.

Buprenorphine abuse in India : an update.

Abstract: This study reviews the available Indian literature on buprenorphine abuse. Buprenorphine was introduced in 1986; the abuse, first noticed in 1987, increased rapidly till 1994, and then decreased gradually. Initiated through other addicts and medical practitioners, the abuse was mostly as a cheap, easily and legally available substitute for opioids. The typical young adult male abuser used an intravenous cocktail with diazepam, pheneramine or promethazine for a better kick. The withdrawal syndrome was typical of the opioids and without an expected delayed onset. Complications of pseudoaneurysm and recurrent koro in repeated withdrawal were reported. Buprenorphine as a detoxifying agent for opioids reportedly gave better symptom control in the first week but high rates of dependence induction were reported. The Indian data tends to caution against the Western enthusiasm to use buprenorphine for detoxification or maintenance of opioid abusers.

Chronic pain during dialysis. Pharmacologic therapy and its costs

Abstract: Background There is very little research into the problem of chronic pain in dialysed patients, despite the fact that pain is a widely diffused phenomena amongst these patients. This work proposes to evaluate the intensity of pain, supply a scale of levels of intervention, with an indication of the consumption and relative costs of pharmacological therapies. Methods 37 out of 100 patients undergoing haemodialysis suffer chronic pain. Aetiological research has shown that osteoarticular pain (24 cases), is the most common, peripheral vascular pain (3 cases), is subjectively and indirectly considered to be the most serious form. Nine cases have presented pain of a neuromuscular origin, whilst one case of a neoplastic origin. The degree of personal invalidism shows serious invalidism in 11 cases. Results The therapeutic file that forsaw four levels of pharmacological intervention (1st levels: FANS, 2nd level: Codeine+paracetamol, 3rd level: Buprenorphine, 4th level: Morphine for os), accompanied by instrumental and pharmacological support intervention, has proved to be indispensable in confronting the problem. Through pharmacy data, we have noticed a progressive increase over the year in the use of analgesic medicines, of which we can confirm the effectiveness, tolerability, low level of side-effects, at low costs. Conclusions In our opinion chronic pain in dialysed patients should not be neglected. The perfection of diagnostic techniques, the discovery of pain-killers with reduced side-effects, the multidisciplinary approach, and reduced costs of treatment, are all valid arguments in favour of an intervention that improves the quality of life of these patients, already so compromised by the nature of the illness itself.

Methods of providing sustained treatment with opioids

Abstract: A method of effectively treating pain in humans is achieved by administering buprenorphine in accordance with first order kinetics over an initial three-day dosing interval, such that a maximum plasma concentration from about 20 pg/ml to about 1052 pg/ml is attained, and thereafter maintaining the administration of buprenorphine for at least an addition two-day dosing interval in accordance with substantially zero order kinetics, such that the patients experience analgesia throughout the at least two-day additional dosing interval.