Buprenorphine: duration of blockade of effects of intramuscular hydromorphone

doi:10.1016/0376-8716(94)90121-X

Drug and Alcohol Dependence

Volume 35, Issue 2, April 1994, Pages 141-149

https://doi.org/10.1016/0376-8716(94)90121-X Get rights and content

Abstract

Six opioid-dependent in-patients were maintained on daily sublingual doses of buprenorphine at 2, 6, and 12 mg/day for five days at each dose in a randomized, balanced sequence. Placebo buprenorphine was substituted for the next three days, and challenge doses of the mu agonist hydromorphone were administered on the three days. Planned comparisons in a 3-factor ANOVA showed dose-dependent hydromorphone effects, significant blockade of ‘high’ by the 12 mg buprenorphine dose, and no differences on hydromorphone-induced ‘high’ across 72 h of active buprenorphine. The data suggest that the blockade by buprenorphine of ‘high’ persists for at least 72 h after the last dose of buprenorphine.

References (23)

J.W. Lewis
Buprenorphine
Drug Alcohol Depend.
(1985)
L. Amass et al.
Administering twice the daily buprenorphine dose suppresses opioid withdrawal for 48 h in opioid-dependent humans
W.K. Bickel et al.
Buprenorphine: dose-related blockade of opioid challenge effects in opioid dependent humans
J. Pharmacol. Exp. Ther.
(1988)
W.K. Bickel et al.
A clinical trial of buprenorphine: comparison with methadone in the detoxification of heroin addicts
Clin. Pharmacol. Ther.
(1988)
P.J. Fudala et al.
Use of buprenorphine in the treatment of opioid addiction. II. Physiologic and behavioral effects of daily and alternate-day administration and abrupt withdrawal
Clin. Pharmacol. Ther.
(1990)
T.J. Gal
Naloxone reversal of buprenorphine-induced respiratory suppression
Clin. Pharmacol. Ther.
(1989)
E.R. Girden
ANOVA: repeated measures
D.R. Jasinski et al.
Human pharmacology and abuse potential of the analgesic buprenorphine
Arch. Gen. Psychiatry
(1978)
D.R. Jasinski et al.
Clonidine in morphine withdrawal: differential effects on signs and symptoms
Arch. Gen. Psychiatry
(1985)
R.E. Johnson et al.
A controlled trial of buprenorphine treatment for opioid dependence
J. Am. Med. Assoc.
(1992)

M. Keeri-Szanto

Anesthesia time/dose curves in the use of hydromorphone surgical anaesthesia and postoperative pain relief in comparison to morphine

Can. Anaesth. Soc. J.

(1976)

Cited by (56)

Trauma treatment for veterans in buprenorphine maintenance treatment for opioid use disorder
2019, Addictive Behaviors
Citation Excerpt :
Medication-assisted treatments (MAT), including buprenorphine or buprenorphine/naloxone, methadone, and injectable naltrexone, are the most effective treatments for OUD, and are associated with significant reductions in morbidity, mortality, and spread of infectious disease (e.g., Thomas et al., 2014; van den Brink & Haasen, 2006). Buprenorphine is a partial opioid agonist that blocks the effects of other opioids (Rosen et al., 1994), thus reducing illicit use during treatment (Thomas et al., 2014; Weiss et al., 2011). The Veterans Health Administration (VHA), which is the largest healthcare system in the country, has made the use of pharmacotherapies to treat OUD a priority, and now includes rates of those on MAT in standard measures of performance (Manhapra, Quinones, & Rosenheck, 2016; Wyse et al., 2018).
Opioid use disorder (OUD) rates are high among veterans. PTSD is also prevalent among veterans; those with comorbidity have worse outcomes than those without comorbidity. This study assessed buprenorphine retention rates in veterans initiating OUD treatment, comparing veterans without PTSD to veterans with PTSD who were receiving versus not receiving concurrent trauma treatment.
This retrospective chart review examined consecutive referrals to buprenorphine maintenance (N = 140). PTSD diagnosis was identified by chart review and retention was defined as continuous buprenorphine maintenance 6-months post-admission. Logistic regression analyses compared buprenorphine retention for veterans without PTSD and PTSD-diagnosed veterans who received concurrent trauma treatment to a reference group of PTSD-diagnosed veterans who did not receive trauma treatment. Models adjusted for opioid type, age, and service-connected status.
Sixty-seven (47.9%) buprenorphine-seeking veterans carried a PTSD diagnosis; only 31.3% (n = 21) received trauma treatment while in buprenorphine maintenance, with 11.9% (n = 8) receiving evidence-based psychotherapy for PTSD. Among PTSD-diagnosed veterans who received trauma treatment, 90.5% (n = 19/21) were in buprenorphine maintenance at 6-months, compared to 23.9% (n = 11/46) of PTSD-diagnosed veterans without trauma treatment, and 46.6% (n = 34/73) of veterans without PTSD. In the full model, veterans with trauma treatment had 43.36 times greater odds of remaining in buprenorphine treatment than the reference group.
Most PTSD-diagnosed veterans in buprenorphine treatment were not receiving trauma treatment. Those receiving concurrent trauma treatment had better retention, suggesting OUD and trauma can be simultaneously addressed. Future clinical trials should investigate trauma-focused treatment for veterans with comorbid PTSD who are seeking buprenorphine for OUD.
Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: Implications for clinical use and policy
2014, Drug and Alcohol Dependence
Citation Excerpt :
Sublingual BUP has been shown to dose-dependently decrease the reinforcing effects of heroin (Comer et al., 2001, 2005; Mello and Mendelson, 1980; Mello et al., 1982) and hydromorphone (Greenwald et al., 2002), consistent with reductions of opioid use in outpatient clinical trials (Johnson et al., 1995; Ling et al., 1998; Schottenfeld et al., 1993). Furthermore, many studies have reported BUP dose-dependent attenuation of the subjective effects of opioids (Bickel et al., 1988; Jasinski et al., 1978; Rosen et al., 1994; Schuh et al., 1999; Teoh et al., 1994; Walsh et al., 1995b). BUP also dose-dependently suppress opioid withdrawal symptoms in human laboratory studies (e.g., Greenwald et al., 2003) and outpatient trials (Fudala et al., 1990; Kuhlman et al., 1998), although the latter may be confounded by uncontrolled opioid use.
Sublingual formulations of buprenorphine (BUP) and BUP/naloxone have well-established pharmacokinetic and pharmacodynamic profiles, and are safe and effective for treating opioid use disorder. Since approvals of these formulations, their clinical use has increased. Yet, questions have arisen as to how BUP binding to mu-opioid receptors (μORs), the neurobiological target for this medication, relate to its clinical application. BUP produces dose- and time-related alterations of μOR availability but some clinicians express concern about whether doses higher than those needed to prevent opioid withdrawal symptoms are warranted, and policymakers consider limiting reimbursement for certain BUP dosing regimens.
We review scientific data concerning BUP-induced changes in μOR availability and their relationship to clinical efficacy.
Withdrawal suppression appears to require ≤50% μOR availability, associated with BUP trough plasma concentrations ≥1 ng/mL; for most patients, this may require single daily BUP doses of 4 mg to defend against trough levels, or lower divided doses. Blockade of the reinforcing and subjective effects of typical doses of abused opioids require <20% μOR availability, associated with BUP trough plasma concentrations ≥3 ng/mL; for most individuals, this may require single daily BUP doses >16 mg, or lower divided doses. For individuals attempting to surmount this blockade with higher-than-usual doses of abused opioids, even larger BUP doses and <10% μOR availability would be required.
For these reasons, and given the complexities of studies on this issue and comorbid problems, we conclude that fixed, arbitrary limits on BUP doses in clinical care or limits on reimbursement for this care are unwarranted.
The association between outpatient buprenorphine detoxification duration and clinical treatment outcomes: A review
2011, Drug and Alcohol Dependence
Citation Excerpt :
This may be related to buprenorphine's long plasma half-life and slow dissociation from the receptor (Bickel et al., 1988a; Bullingham et al., 1980; Fudala et al., 1990; Hambrook and Rance, 1976; Jasinski et al., 1978). Second, buprenorphine blocks the effects of exogenously administered opioids, and can potentially slow or prevent relapse to illicit opioids from occurring (Jasinski et al., 1978; Mello et al., 1982; Rosen et al., 1994; Walsh et al., 1995). Third, buprenorphine has a ceiling on its agonist effects that reduces the risk for buprenorphine-related overdose, making it a good candidate for use in outpatient settings (Banks, 1979; Jasinski et al., 1978; Lewis, 1985; Mello and Mendelson, 1980; Walsh et al., 1994, 1995).
The association between buprenorphine taper duration and treatment outcomes is not well understood. This review evaluated whether duration of outpatient buprenorphine taper is significantly associated with treatment outcomes.
Studies that were published in peer-reviewed journals, administered buprenorphine as an outpatient taper to opioid-dependent participants, and provided data on at least one of three primary treatment outcome measures (opioid abstinence, retention, peak withdrawal severity) were reviewed. Primary treatment outcomes were evaluated as a function of taper duration using hierarchical linear regressions with pre-taper maintenance duration as a cofactor.
Twenty-eight studies were reviewed. Taper duration significantly predicted percent of opioid-negative samples provided during treatment, however pre-taper maintenance period predicted percent participants abstinent on the final day of treatment. High rates of relapse were reported. No significant association between taper duration and retention in treatment or peak withdrawal severity was observed.
The data reviewed here suggest taper duration is associated with opioid abstinence achieved during detoxification but not with other markers of treatment outcome. The reviewed studies varied widely on several parameters (e.g., frequency of urinalysis testing, provision of ancillary medications) that may influence treatment outcome and thus could have interfered with the ability to identify relationships between taper duration and outcomes. Future studies evaluating opioid detoxification should utilize rigorous experimental methods and report a wider range of outcome measures in order to help advance our understanding of the association between taper duration and treatment outcomes.
Pharmacological aspects of the buprenorphine-naloxona treatment programmes
2008, Trastornos Adictivos
El objetivo del presente trabajo es realizar una revisión conceptual sobre los principales aspectos farmacológicos que fundamentan el uso clínico de la buprenorfina/naloxona.
Se realiza una búsqueda bibliográfica y se revisan las principales guías clínicas de buena práctica sobre el tratamiento con buprenorfina y buprenorfina/naloxona. Se seleccionan las recomendaciones coincidentes y se realiza una síntesis actualizada desde una orientación clínica práctica.
La buprenorfina/naloxona es un producto con un perfil farmacológico eficaz y seguro para el tratamiento de la dependencia de opiáceos. Como agonista parcial de los receptores opiáceos (μ y antagonista de los receptores opiáceos (κ, ofrece ciertas ventajas para un determinado grupo de pacientes dependientes de los opiáceos, a pesar de que la metadona seguirá siendo el fármaco de primera elección para la mayoría. La fase de inducción es un proceso seguro y cómodo para la mayoría de los pacientes, siendo fundamental una correcta y suficiente información. Se constata una estrecha relación entre el tiempo del paciente en tratamiento y los resultados del programa. Debido a su prolongada vida media, la retirada del fármaco es cómoda para el paciente, sin la presencia de síntomas de abstinencia significativos.
La buprenorfina/naloxona va a ocupar el «espacio» existente entre los programas de tratamiento con agonistas (metadona) y los denominados «programas libres de drogas». Se trata de un fármaco eficaz y seguro que debe emplearse en el contexto de un programa de intervención psicosocial más amplio.
The aim of this work is to carry out a conceptual review of the main pharmacological aspects on which the clinical use of buprenorphine/ naloxone is based.
A bibliographical search is done, and the major clinical guides are reviewed for good practice in treatment with buprenorphine and buprenorphine/nolaxone. The recommendations they have in common are selected and an updated synthesis is carried out from a clinical practice viewpoint.
Buprenorphine/naloxone has a safe and efficient pharmacological profile for the treatment of dependence on opiates. As a partial agonist of the opiate (μ receptors and antagonist of the opiate (κ receptors, they offer certain advantages for a particular group of opiate addicts, even though methadone will continue to be the first choice for most such patients. The induction phase, in which sufficient, and correct information is essential, is a safe and easy process for most patients. The time the patient is treated and the programme results are closely related. Due to the prolonged half-life of this medicament, there are no significant withdrawal symptoms when patients end treatment.
Buprenorphine/naloxone will cover the existing «gap» between treatment programmes using agonist (methadone) and the so-called «drugfree programmes». It is a safe and effective medicament that should be used in the context of a wider programme of psycho-social intervention.
Buprenorphine Duration of Action: Mu-opioid Receptor Availability and Pharmacokinetic and Behavioral Indices
2007, Biological Psychiatry
Buprenorphine (BUP) is effective in the treatment of opioid dependence when given on alternating days, probably as a result of long-lasting occupation of μ opioid receptors (μORs). This study examined the duration of action of BUP at μORs and correlations with pharmacokinetic and pharmacodynamic outcomes in 10 heroin-dependent volunteers.
Availability of μOR (measured with positron emission tomography and [¹¹C]-carfentanil), plasma BUP concentration, opioid withdrawal symptoms, and blockade of hydromorphone (HYD; heroin-like agonist) effects were measured at 4, 28, 52, and 76 hours after omitting the 16 mg/d dose of BUP in a study reported elsewhere.
Relative to heroin-dependent volunteers maintained on BUP placebo, whole-brain μOR availability was 30%, 54%, 67%, and 82% at 4, 28, 52, and 76 hours after BUP. Regions of interest showed similar effects. Plasma concentrations of BUP were time dependent, as were withdrawal symptoms, carbon dioxide sensitivity and extent of HYD blockade. Availability of μOR was also correlated with BUP plasma concentration, withdrawal symptoms, and HYD blockade.
Together with our previous findings, it appears that μOR availability predicts changes in pharmacokinetic and pharmacodynamic measures and that about 50%–60% BUP occupancy is required for adequate withdrawal symptom suppression (in the absence of other opioids) and HYD blockade.
Recent advances in the treatment of opiate addiction
2005, Clinical Neuroscience Research
Advances in the modern treatment of opiate addiction are the result of an evolutionary process often attributed to the introduction of methadone maintenance in the 1960s. The underpinnings and the forces that shaped these advances, however, date back to the rise of the prohibition movement at the turn of the century, which culminated in passage of the Harrison Narcotic Act, signaling a major shift in US social attitudes towards heroin addicts and their addiction. Subsequent US social and political attitudes have shaped the course of treatment practices in parallel with scientific advances and pharmacological developments, from the establishment of methadone treatment in specialized narcotics treatment clinics to the introduction of buprenorphine and the concomitant legislative mandate that made it available to general physicians, reflecting again the current societal attitude. While pharmacological progress may appear to be related to scientific advancement, the major driving force behind the direction of treatment development and its implementation into the treatment community is deeply ingrained in the concurrent evolution of societal attitudes and political policies. Moreover, the undisputed US dominance in science and politics lends global impetus to these developments.

View all citing articles on Scopus

View full text

Buprenorphine: duration of blockade of effects of intramuscular hydromorphone

Abstract

Drug Alcohol Depend.

Administering twice the daily buprenorphine dose suppresses opioid withdrawal for 48 h in opioid-dependent humans

Buprenorphine: dose-related blockade of opioid challenge effects in opioid dependent humans

J. Pharmacol. Exp. Ther.

A clinical trial of buprenorphine: comparison with methadone in the detoxification of heroin addicts

Clin. Pharmacol. Ther.

Use of buprenorphine in the treatment of opioid addiction. II. Physiologic and behavioral effects of daily and alternate-day administration and abrupt withdrawal

Clin. Pharmacol. Ther.

Naloxone reversal of buprenorphine-induced respiratory suppression

Clin. Pharmacol. Ther.

ANOVA: repeated measures

Human pharmacology and abuse potential of the analgesic buprenorphine

Arch. Gen. Psychiatry

Clonidine in morphine withdrawal: differential effects on signs and symptoms

Arch. Gen. Psychiatry

A controlled trial of buprenorphine treatment for opioid dependence

J. Am. Med. Assoc.

Anesthesia time/dose curves in the use of hydromorphone surgical anaesthesia and postoperative pain relief in comparison to morphine

Can. Anaesth. Soc. J.