Acute administration of buprenorphine in humans: partial agonist and blockade effects.
ABSTRACT Buprenorphine, a mixed opioid agonist-antagonist, is being investigated as a treatment for opioid dependence. This study compared the acute subjective and physiological effects of sublingual buprenorphine to those of p.o. methadone over a wide range of doses and compared the ability of both drugs to alter the effects of an opioid challenge. Male inpatient volunteers (n = 9) with histories of opioid abuse participated in this double-blind, double-dummy study. Sublingual buprenorphine (0, 0.5, 2, 8, 16 and 32 mg) and p.o. methadone (3.75, 15 and 60 mg) were administered once weekly according to a Latin-square design, and subjects were monitored on a variety of physiological and subjective measures. Twenty-four hours later, subjects were tested with ascending doses of i.m. hydromorphone (0, 1 and 4 mg) given 45 min apart. Buprenorphine and methadone produced typical opioid agonist effects of long duration, including pupillary constriction, respiratory depression and elevations on subject-rated and observer-rated indices of euphoria, sedation and opioid-like symptoms. The buprenorphine dose-effect curves were nonlinear and maximal effects for most physiological and subjective measures were observed between 4 and 8 mg, with no greater effects observed at higher doses. The methadone dose-effect curves were linear across the range of doses tested. High doses of buprenorphine and methadone both attenuated the response to hydromorphone challenge 24 hr later. These data indicate that there is a ceiling on the effects of buprenorphine in humans that may reduce its abuse liability and increase its safety, and indicate that opioid blockade occurs after acute administration of buprenorphine or methadone.
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ABSTRACT: Increasing rates of maternal opioid use during pregnancy and neonatal withdrawal, termed neonatal abstinence syndrome (NAS), are public health concerns. Prenatal buprenorphine maintenance treatment (BMT) versus methadone maintenance treatment (MMT) may improve neonatal outcomes, but associations vary. To summarize evidence, we used a random-effects meta-analysis model and estimated summary measures of BMT versus MMT on several outcomes. Sensitivity analyses evaluated confounding, publication bias, and heterogeneity. Subjects were 515 neonates whose mothers received BMT and 855 neonates whose mothers received MMT and who were born from 1996 to 2012 and who were included in 12 studies. The unadjusted NAS treatment risk was lower (risk ratio = 0.90, 95% confidence interval (CI): 0.81, 0.98) and mean length of hospital stay shorter (-7.23 days, 95% CI: -10.64, -3.83) in BMT-exposed versus MMT-exposed neonates. In treated neonates, NAS treatment duration was shorter (-8.46 days, 95% CI: -14.48, -2.44) and morphine dose lower (-3.60 mg, 95% CI: -7.26, 0.07) in those exposed to BMT. BMT-exposed neonates had higher mean gestational age and greater weight, length, and head circumference at birth. Fewer women treated with BMT used illicit opioids near delivery (risk ratio = 0.44, 95% CI: 0.28, 0.70). Simulations suggested that confounding by indication could account for some of the observed differences. Prenatal BMT versus MMT may improve neonatal outcomes, but bias may contribute to this protective association. Further evidence is needed to guide treatment choices.American Journal of Epidemiology 08/2014; 180(7). DOI:10.1093/aje/kwu190 · 4.98 Impact Factor
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ABSTRACT: 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.Drug and Alcohol Dependence 08/2014; DOI:10.1016/j.drugalcdep.2014.07.035 · 3.28 Impact Factor