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American Journal of Veterinary Research Jun 2022To assess the pharmacokinetics, clinical efficacy, and adverse effects of injectable methadone with the pharmacokinetic enhancer fluconazole (methadone-fluconazole),...
Long-acting injectable methadone (methadone-fluconazole) provides safe and effective postoperative analgesia in a randomized clinical trial for dogs undergoing soft tissue surgery.
OBJECTIVE
To assess the pharmacokinetics, clinical efficacy, and adverse effects of injectable methadone with the pharmacokinetic enhancer fluconazole (methadone-fluconazole), compared with the standard formulation of injectable methadone, in dogs after ovariohysterectomy. We hypothesized that 2 doses of methadone-fluconazole would provide 24 hours of postoperative analgesia.
ANIMALS
3 purpose-bred dogs (pharmacokinetic preliminary study) and 42 female dogs from local shelters (clinical trial) were included.
PROCEDURES
Pharmacokinetics were preliminarily determined. Clinical trial client-owned dogs were blocked by body weight into treatment groups: standard methadone group (methadone standard formulation, 0.5 mg/kg, SC, q 4 h; n = 20) or methadone-fluconazole group (0.5 mg/kg methadone with 2.5 mg/kg fluconazole, SC, repeated once at 6 h; n = 22). All dogs also received acepromazine, propofol, and isoflurane. Surgeries were performed by experienced surgeons, and dogs were monitored perioperatively using the Glasgow Composite Measure Pain Scale-Short Form (CMPS-SF) and sedation scales. Evaluators were masked to treatment.
RESULTS
Findings from pharmacokinetic preliminary studies supported that 2 doses of methadone-fluconazole provide 24 hours of drug exposure. The clinical trial had no significant differences in treatment failures or postoperative CMPS-SF scores between treatments. One dog (methadone-fluconazole group) had CMPS-SF > 6 and received rescue analgesia. All dogs had moderate sedation or less by 1 hour (methadone-fluconazole group) or 4 hours (standard methadone group) postoperatively. Sedation was completely resolved in all dogs the day after surgery.
CLINICAL RELEVANCE
Methadone-fluconazole with twice-daily administration was well tolerated and provided effective postoperative analgesia for dogs undergoing ovariohysterectomy. Clinical compliance and postoperative pain control may improve with an effective twice-daily formulation.
Topics: Analgesia; Analgesics, Opioid; Animals; Dog Diseases; Dogs; Female; Fluconazole; Hysterectomy; Methadone; Ovariectomy; Pain, Postoperative
PubMed: 35895789
DOI: 10.2460/ajvr.22.01.0014 -
Substance Abuse 2015Despite evidence of low transfer of methadone into breast milk and the potential physical and psychological benefits that breastfeeding offers for methadone-exposed...
BACKGROUND
Despite evidence of low transfer of methadone into breast milk and the potential physical and psychological benefits that breastfeeding offers for methadone-exposed mothers and infants, the rate of breastfeeding initiation in this population is about half that reported nationally. This study describes the perceptions surrounding breastfeeding decisions and management among pregnant and postpartum women taking methadone.
METHODS
Seven pregnant women and 4 postpartum women enrolled in methadone maintenance programs participated in semistructured, audiotaped interviews and focus groups, respectively, about their breastfeeding experiences. Transcripts were analyzed and coded using qualitative content analysis.
RESULTS
Three major content categories were identified: (1) fears, barriers, and misconceptions about breastfeeding while taking methadone; (2) motivation and perceived benefits of breastfeeding; and (3) sources of information, support, and anxiety about general breastfeeding management and breastfeeding while taking methadone. Lack of support from the health care community and misinformation about the dangers of combining breastfeeding and methadone therapy represented significant, yet modifiable, barriers to breastfeeding success in methadone-exposed women.
CONCLUSIONS
Interventions to increase the prevalence of breastfeeding among women taking methadone should address identified logistical, educational, and psychological barriers and consider inclusion of women themselves, partners, peers, and clinicians. In particular, clinicians who care for methadone-exposed mothers and infants should be educated on therapeutic communication, up-to-date breastfeeding contraindications, and the health benefits of breastfeeding in this population.
Topics: Adolescent; Adult; Analgesics, Opioid; Breast Feeding; Contraindications; Female; Focus Groups; Health Knowledge, Attitudes, Practice; Humans; Methadone; Mothers; Opiate Substitution Treatment; Pregnancy; Young Adult
PubMed: 24702686
DOI: 10.1080/08897077.2014.902417 -
The Western Journal of Medicine May 1990We describe the historical underpinnings of negative attitudes towards methadone and how these affect medical decisions. Current developments have increased the... (Review)
Review
We describe the historical underpinnings of negative attitudes towards methadone and how these affect medical decisions. Current developments have increased the understanding of the origins of opioid addiction, such as how receptor system dysfunction may affect the ability to remain abstinent once out of treatment. Specialized topics include the pregnant addict, the role of methadone maintenance in limiting the spread of the acquired immunodeficiency syndrome, and patients with a dual diagnosis. We also describe issues that arise when methadone is used in conjunction with prescribed or abused drugs, noting pharmacologic alternatives and adjuncts to methadone treatment. Finally, we comment on treatment issues such as methadone patients in 12-step programs and the growing legitimacy of this treatment method.
Topics: Acquired Immunodeficiency Syndrome; Attitude of Health Personnel; Cocaine; Drug Interactions; Ethanol; Female; Heroin Dependence; Humans; Methadone; Opioid-Related Disorders; Pregnancy; Substance Withdrawal Syndrome
PubMed: 2190427
DOI: No ID Found -
Molecules (Basel, Switzerland) Nov 2022(1) Background: Methadone, along with buprenorphine, is the most commonly used drug for the treatment of opioid dependence. This study aimed to analyze methadone and its...
(1) Background: Methadone, along with buprenorphine, is the most commonly used drug for the treatment of opioid dependence. This study aimed to analyze methadone and its major metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenyl pyrrolidine (EDDP), in the urine and plasma of opiate addicts. The study group consisted of drug users voluntarily admitted to the detoxification center C.E.T.T.T. "St. Stelian" of Bucharest. Secondly, the study aimed to identify whether urine or plasma provides better results for the proposed method. (2) Methods: A GC-MS method, using an internal standard (diphenylamine) in the FULL-SCAN and SIM modes of operation and using the m/z = 72 ion for methadone and the m/z = 277 ion for EDDP, combined with a liquid-liquid extraction procedure was performed. (3) Results: The applied procedure allows the detection and quantification of methadone in both urine and plasma samples. EDDP was identified in patients with higher levels of methadone. Higher levels of methadone were detected in urine than in plasma samples. (4) Conclusions: This procedure can be used in clinical laboratories for the rapid determination of methadone levels in urine rather than in plasma. The procedure can be applied for the monitoring of methadone substitution treatment.
Topics: Humans; Methadone; Gas Chromatography-Mass Spectrometry; Buprenorphine; Opioid-Related Disorders; Pyrrolidines
PubMed: 36500452
DOI: 10.3390/molecules27238360 -
British Journal of Pharmacology Apr 2023Opioid use disorder is a worldwide societal problem and public health burden. Strategies for treating opioid use disorder can be divided into those that target the... (Review)
Review
Opioid use disorder is a worldwide societal problem and public health burden. Strategies for treating opioid use disorder can be divided into those that target the opioid receptor system and those that target non-opioid receptor systems, including the dopamine and glutamate receptor systems. Currently, the clinical drugs used to treat opioid use disorder include the opioid receptor agonists methadone and buprenorphine, which are limited by their abuse liability, and the opioid receptor antagonist naltrexone, which is limited by poor compliance. Therefore, the development of effective medications with lower abuse liability and better potential for compliance is urgently needed. Based on recent advances in the understanding of the neurobiological mechanisms underlying opioid use disorder, potential treatment strategies and targets have emerged. This review focuses on the progress made in identifying potential targets and developing medications to treat opioid use disorder, including progress made by our laboratory, and provides insights for future medication development. LINKED ARTICLES: This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.
Topics: Humans; Opioid-Related Disorders; Analgesics, Opioid; Methadone; Buprenorphine; Naltrexone
PubMed: 34128238
DOI: 10.1111/bph.15592 -
Stem Cell Research Dec 2020Prenatal opioids exposure can lead to both neonatal abstinence syndrome in newborns and neurological deficits later in life. Although opioids have been well studied in...
Prenatal opioids exposure can lead to both neonatal abstinence syndrome in newborns and neurological deficits later in life. Although opioids have been well studied in general, the cellular and molecular mechanisms by which opioids affect human fetal brain development has not been well understood. In this work, we have taken advantage of a human 3D-brain cortical organoid (hCO) that facilitated enormously the investigation of early human brain development. Using imaging, immunofluorescence, multi-electrode array (MEA) and patch clamp recording techniques, we have investigated the effect of methadone, a frequently used opioid during pregnancy, on early neural development, including neuronal growth, neural network activity and synaptic transmission in hCOs. Our results demonstrated that methadone dose-dependently halted the growth of hCOs and induced organoid disintegration after a prolonged exposure. In addition, methadone dose-dependently suppressed the firing of spontaneous action potentials in hCOs and this suppression could be reversed upon methadone withdrawal in hCOs treated with lower dosages. Further investigation using patch clamp whole cell configuration revealed that, at clinically relevant concentrations, methadone decreased the frequency and amplitude of excitatory postsynaptic currents in neurons, indicating a critical role of methadone in weakening synaptic transmission in neural networks in hCOs. In addition, methadone significantly attenuated the voltage-dependent Na current in hCOs. We conclude that methadone interrupts neural growth and function in early brain development.
Topics: Action Potentials; Female; Humans; Infant, Newborn; Methadone; Organoids; Patch-Clamp Techniques; Pregnancy; Synaptic Transmission
PubMed: 33137567
DOI: 10.1016/j.scr.2020.102065 -
Bulletin of the New York Academy of... 1990
Topics: Ambulatory Care Facilities; Humans; Methadone; New York City; Substance-Related Disorders
PubMed: 2364219
DOI: No ID Found -
Anesthesiology Oct 2023
Topics: Methadone; Analgesics
PubMed: 37698432
DOI: 10.1097/ALN.0000000000004681 -
Electrophoresis Sep 2021The enantioselectivity of the pharmacokinetics of methadone was investigated in anesthetized Shetland ponies after a single intravenous (0.5 mg/kg methadone...
The enantioselectivity of the pharmacokinetics of methadone was investigated in anesthetized Shetland ponies after a single intravenous (0.5 mg/kg methadone hydrochloride; n = 6) or constant rate infusion (0.25 mg/kg bolus followed by 0.25 mg/kg/h methadone hydrochloride; n = 3) administration of racemic methadone. Plasma concentrations of l-methadone and d-methadone and their major metabolites, l- and d-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), respectively, were analyzed by CE with highly sulfated γ-cyclodextrin as chiral selector and electrokinetic analyte injection from liquid/liquid extracts prepared at alkaline pH. In both trials, the d-methadone concentrations were lower than those of l-methadone and the d-EDDP levels were lower than those of L-EDDP. For the case of a single intravenous bolus injection, the plasma concentration versus time profile of methadone enantiomers was analyzed with a two-compartment pharmacokinetic model. l-methadone showed a slower elimination rate constant, a lower body clearance, and a smaller steady-state volume of distribution than d-methadone. d-methadone and d-EDDP were eliminated faster than their respective l-enantiomers. This is the first study that outlines that the disposition of racemic methadone administered to anesthetized equines is enantioselective.
Topics: Animals; Electrophoresis, Capillary; Horses; Methadone; Pyrrolidines; Stereoisomerism
PubMed: 33978252
DOI: 10.1002/elps.202100115 -
The American Journal of Psychiatry Sep 2021The authors conducted a scoping review to survey the evidence landscape for studies that assessed outcomes of treating patients with opioid use disorder with methadone...
OBJECTIVE
The authors conducted a scoping review to survey the evidence landscape for studies that assessed outcomes of treating patients with opioid use disorder with methadone in office-based settings.
METHODS
Ovid MEDLINE and the Cochrane Database of Systematic Reviews were searched, and reference lists were reviewed to identify additional studies. Studies were eligible if they focused on methadone treatment in office-based settings conducted in the United States or other highly developed countries and reported outcomes (e.g., retention in care). Randomized trials and controlled observational studies were prioritized; uncontrolled and descriptive studies were included when stronger evidence was unavailable. One investigator abstracted key information, and a second verified data. A scoping review approach broadly surveyed the evidence, and therefore study quality was not rated formally.
RESULTS
Eighteen studies of patients treated with office-based methadone were identified, including six trials, eight observational studies, and four additional articles discussing use of pharmacies to dispense methadone. Studies on office-based methadone treatment, including primary care-based dispensing, were limited but consistently found that stable methadone patients valued office-based care and remained in care with low rates of drug use; outcomes were similar compared with stable patients in regular care. Office-based methadone treatment was associated with higher treatment satisfaction and quality of life. Limitations included underpowered comparisons and small samples.
CONCLUSIONS
Limited research suggests that office-based methadone treatment and pharmacy dispensing could enhance access to methadone treatment for patients with opioid use disorder without adversely affecting patient outcomes and, potentially, inform modifications to federal regulations. Research should assess the feasibility of office-based care for less stable patients.
Topics: Drug Prescriptions; Humans; Methadone; Narcotics; Opioid-Related Disorders; Pharmacies
PubMed: 34315284
DOI: 10.1176/appi.ajp.2021.20101548