DOCSLIB.ORG

Prediction of Drug Interactions with Methadone, Buprenorphine and Oxycodone from in Vitro Inhibition of Metabolism

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Prediction of Drug Interactions with Methadone, Buprenorphine and Oxycodone from in Vitro Inhibition of Metabolism The author(s) shown below used Federal funds provided by the U.S. Department of Justice and prepared the following final report: Document Title: Prediction of Drug Interactions with Methadone, Buprenorphine and Oxycodone from In Vitro Inhibition of Metabolism Author(s): David E. Moody, Ph.D. Document No.: 250127 Date Received: July 2016 Award Number: 2011-DN-BX-K532 This report has not been published by the U.S. Department of Justice. To provide better customer service, NCJRS has made this federally funded grant report available electronically. Opinions or points of view expressed are those of the author(s) and do not necessarily reflect the official position or policies of the U.S. Department of Justice. February 2016 Research and Development in Forensic Toxicology Prediction of drug interactions with methadone, buprenorphine and oxycodone from in vitro inhibition of metabolism Final Technical Report Submitted electronically to: U.S. Department of Justice Office of Justice Programs National Institute of Justice Prepared by: David E. Moody. Ph.D. Director of the Center for Human Toxicology, and Research Professor of Pharmacology and Toxicology [email protected] / 801-581-5117 NIJ Award Number: 2011-DN-BX-K532 Reporting Period: January 1, 2012 to December 31, 2015 Recipient Organization: University of Utah 75 South 2000 East, Room 222 Salt Lake City, UT 84112-8930 Organizational DUNS: 0090953650000 EIN: 876000525 This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s) and do not necessarily reflect the official position or policies of the U.S. Department of Justice. Table of Contents Cover Page …………………………………………………………………………………… 1 Table of Contents ……………………………………………………………………..……… 2 Abstract ……………………………………………………………………………….……… 6 Executive Summary ………………………………………………………………..………… 7 ES 1.0 Introduction ………………………………………………………………………. 7 ES 2.0 Major Goals / Aims …………………………………………………………….… 7 ES 3.0 Accomplishments Under Goals …………………………………………………… 8 ES 3.1 Background …………………………………………………………… 8 ES 3.2 Accomplishments under Aim 1.A - Optimization of Incubation Conditions: HLM …………………………………………………….. 10 ES 3.3 Accomplishments under Aims 2 and 3: HLM Screens, IC50 Determinations and Extrapolations to In Vivo Potency ……………… 10 ES 3.4 Accomplishments under Aims 1B and 4 - Studies on TDI Kinetic Determinations and Follow Up experiments …………………...……. 11 ES 4.0 Conclusions …………………………………………………………………..….. 11 ES 4.1 Summary of Accomplishments …………………………………..….. 11 ES 4.2 Implications for Policy and Practice …………………………………. 12 ES 4.2.1 What is the impact of the project on the criminal justice system? …………………………………………………… 12 ES 4.2.2 How has it contributed to crime laboratories? ………...…. 12 ES 4.3 Implications for Further Research ……………………………………. 12 Technical Report ……………………………………………………………….……………. 13 1.0 Introduction ………………………………………………………………………….. 13 2.0 Major Goals / Aims …………………………………………………………..…….... 15 3.0 Accomplishments Under Goals ……………………………………………………… 16 3.1 Background …………………………………………………………………….......... 16 3.2 Accomplishments under Aim 1.A - Optimization of Incubation Conditions: HLM.... 19 3.2.1 Initial Studies with Oxycodone and Methadone ……………………………… 19 3.2.2 (Re)Optimization of Assays with 20-µM substrate ……………………………….. 20 3.2.3 Background Formation With Use of 20 µM Substrates …………………………. 21 3.2.4 Negative Controls ± Solvent ……………………………………………………………..….. 22 3.2.5 Positive Controls for TDI …………………………………………………………………..… 23 3.3 Accomplishments under Aims 2 and 3: HLM Screens, IC50 Determinations and Extrapolations to In Vivo Potency ………………………………………………..... 23 3.3.1 Methadone and Oxycodone Inhibition by H2-Receptor Antagonists and Proton Pump Inhibitors with Substrate at 2.0-µM ……………………....…. 23 2 This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s) and do not necessarily reflect the official position or policies of the U.S. Department of Justice. 3.3.2 Buprenorphine, Methadone and Oxycodone Inhibition by Azole Antifungal Agents with Substrate at 20-µM ……………………………………….…. 27 3.4 Accomplishments under Aims 1B and 4 - Studies on TDI Kinetic Determinations and Follow Up experiments ………………………………………………………… 33 3.4.1 TDI Positive Controls ………………………………………………………… 33 3.4.2 Determining TDI kinetics for Cimetidine and Different CYP-mediated Pathways ………………………………………………………………….…. 36 3.4.3 TDI and PPI ………………………………………………………………..… 38 3.4.4 Establishing MBI …………………………………………………………….. 41 4.0 Conclusions ……………………………………………………………………..…… 42 4.1 Summary of Accomplishments …………………………………………….… 42 4.2 Implications for Policy and Practice ……………………………………….… 42 4.2.1 What is the impact of the project on the criminal justice system? …... 42 4.2.2 How has it contributed to crime laboratories? ……………………..... 43 4.3 Implications for Further Research …………………………………………… 43 5.0 References ………………………………………………………………………….... 43 6.0 Training and Professional Development Opportunities ……………………….…….. 48 7.0 Dissemination of Results ……………………..……………………..……………..… 49 8.0 Glossary of Abbreviations …………………………………………………………… 50 List of Tables Table 1. Drugs to test for inhibition potential ……………………..…………………..….. 17 Table 2. Optimized Incubation Conditions for Buprenorphine, Methadone and Oxycodone Metabolism Assays ……………………..……………………...…… 21 Table 3. Approximate IC50 Determinations for H2-Receptor Antagonists and Proton Pump Inhibitors Incubated with HLM ± Pre-Incubation ………………………... 24 Table 4. IC50s and Estimates of Ki and In Vivo Inhibitory Potential at Average and 10X Average Plasma Concentrations of Inhibitor ……………………..……………… 25 Table 5. Examples of the Impact of Plasma and Microsome Drug Binding on Calculation of Inhibitory Potential: Oxycodone Metabolism by CYP3A4 …………………... 26 Table 6. Approximate IC50 Determinations for Azole Antifungals Incubated with HLM ± Pre-Incubation ……………………..……………………..…………………….. 28 Table 7. In Vitro Reversible Inhibition of CYP-Mediated Metabolism of Methadone, Buprenorphine and Oxycodone by Azole Antifungal Agents …………………… 30 Table 8. Extrapolation of IC50 Determinations to Ki and Inhibitory Potential at Average and 10 x Average Plasma Concentration of Azole Inhibitors ……………..…….. 32 3 This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s) and do not necessarily reflect the official position or policies of the U.S. Department of Justice. Table 9. IC50 Determination for Proton Pump Inhibitors (PPIs) and Their Metabolites on Buprenorphine Metabolism: Effect of Pre-incubation with Inhibitor …….….. 40 List of Figures Figure 1. Metabolic routes under study with primary cytochrome P450 (CYP450) involved in metabolism indicated ……………………..……………………...… 18 Figure 2. Hypothetical effect of reversible versus irreversible inhibitors on the plasma concentration of a target drug during a pharmacokinetic drug interaction ……... 19 Figure 3. Initial optimization of oxycodone metabolism in HLM ………………………… 20 Figure 4. Buprenorphine utilization and norbuprenorphine formation in HLM, CYP3A4 and CYP2C8 incubated with 20-µM buprenorphine ……………………………. 21 Figure 5. Amount of metabolite detected in HLM that were incubated for 0-time with no inhibitors added (i.e., background samples) ……………………………………. 22 Figure 6. Effect of addition of 1% DMSO and pre-incubation on the activity of the negative controls to which no inhibitor is added ………………………………... 22 Figure 7. Effect of pre-incubation on inhibition by the positive controls 5 µM troleandromycin (Trol), 5 µM gemfibrozil glucuronide (Gem), 0.5 µM paroxetine (Parox), and 10 µM ThioTEPA …………………………………...… 23 Figure 8. Plot of upper concentration of inhibitor used to not exceed 1% DMSO in incubation versus log of the octanol-water partition coefficient (X Log P3) ….... 28 Figure 9. Inhibition of the CYP450 mediated metabolism using the highest achievable concentration for non-CYP3A4 pathways, and highest concentration used in IC50 determinations for CYP3A4 pathways ……………………………………... 29 Figure 10. Ranking of IC50 determinations for CYP3A4 mediated pathways …………….... 31 . Figure 11. Determination of kinetics for MBI of CYP3A4 metabolism of buprenorphine by troleandomycin (TAO) …………………………………………………….… 34 Figure 12. Determination of kinetics for MBI by TAO of CYP3A4 metabolism of oxycodone to noroxycodone, racemic methadone to R-EDDP, and racemic methadone to S-EDDP ……………………..……………………..…………..… 35 Figure 13. Determination of kinetics for MBI by gemfibrozil glucuronide of CYP2C8 metabolism of buprenorphine …………………………………………….…….. 36 4 This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s) and do not necessarily reflect the official position or policies of the U.S. Department of Justice. Figure 14. Inhibition of buprenorphine (20-µM) metabolism in HLM by the H2-receptor antagonists ± 15 minute pre-incubation ……………………..………………….. 36 Figure 15. Inhibition of 20-µM oxycodone and methadone metabolism ± 15 minute pre-incubation with cimetidine ………………………………………………….. 37 Figure 16. Kobs versus inhibitor concentration nonlinear regression plots for TDI by cimetidine ……………………..……………………..………………………. 37 Figure
Load more

Recommended publications
  • Expert Review 2
    2021 Expert Committee on Selection and Use of Essential Medicines Application review I.1 Albendazole, mebendazole and praziquantel for the indication of treatment of (item number) taeniid cestode cysts Does the application adequately ☒ Yes address the issue of the public health ☐ need for the medicine? No ☐ Not applicable Comments: The larval stages of three taeniid cestode parasites, Echinococcus granulosus, Echinococcus multilocularis and Taenia solium, produce cysts in humans that are of medical relevance. The diseases caused by these parasitic cysts are called cystic echinococcosis (CE), alveolar echinococcosis (AE), and cysticercosis (being neurocysticercosis (NCC) the most common form) respectively, and they are recognised by WHO as neglected tropical diseases. NCC is mainly a disease of poverty that predominantly affects rural populations in Africa, Asia and Latin America. Access to diagnostic and treatment, to better manage epilepsy and other NCC is a challenge for the people affected in these communities due to the availability and costs of specialised diagnostic and care. Stigma and social discrimination also mean that many people try to “hide” the disease. Briefly summarize the role of the The only real options for treatment of CE are albendazole (ALB) and Mebendazole proposed medicine(s) relative to other (MEB). ALB is the drug of choice as it has better bioavailability. ALB is also preferred to therapeutic agents currently included in MEB, because MEB requires a higher dose and a higher pill burden, for example, an the Model List, or available in the adult patient would require 8 tablets/day of MEB compared with 2 tablets/day ALB. market. ALB and praziquantel ( PZQ) are the only drugs used for the antiparasitic treatment of NCC.
    [Show full text]
  • ( 12 ) United States Patent
    US010376507B2 (12 ) United States Patent (10 ) Patent No. : US 10 , 376 , 507 B2 Srinivasan et al. (45 ) Date of Patent: Aug. 13 , 2019 CRESEMBA® ( isavuconazonium sulfate ) , Highlights of Prescrib (54 ) METHOD OF TREATING A PATIENT WITH ing Information , Label ; Patient Information approved by the U . S . A CYP3A4 SUBSTRATE DRUG Food and Drug Administration ; Astellas Pharma US , Inc. ( Licensed from Basilea Pharmaceutics International Ltd . ) , Illinois, USA , Ini (71 ) Applicant: Bow River LLC , Corona Del Mar , CA tial U . S . Approval: 2015 , Revised Mar. 2015 , Reference ID : 3712237, ( US ) 28 pages . DIFLUCAN® ( fluconazole ), Label ; Patient Information , Reference ( 72 ) Inventors : Sundar Srinivasan , Corona Del Mar, ID : 3650838 , Roerig , Division of Pfizer Inc ., New York , NY, Revised Mar. 2013 , 35 pages. CA (US ) ; Christina Chow , Seattle , WA NIZORAL® (ketoconazole )Label ; Patient Information approved by (US ) the U . S . Food and Drug Administration , Reference ID : 3458324 , Copyright 2014 Janssen Pharmaceuticals, Inc . , New Jersey, USA , ( 73 ) Assignee : BOW RIVER LLC , Corona del Mar , Revised Feb . 2014 , 23 pages . NOXAFIL® (posaconazole ) , Highlights of Prescribing Informa CA (US ) tion , Label ; Patient Information approved by the U . S . Food and Drug Administration ; Copyright © 2006 , 2010 , 2013 , 2014 Merck ( * ) Notice : Subject to any disclaimer , the term of this Sharp & Dohme Corp . , a subsidiary of Merck & Co ., Inc ., New patent is extended or adjusted under 35 Jersey , USA , Revised Sep . 2016 , Reference ID : 3983525, 37 pages . U . S . C . 154 (b ) by 0 days. ORAVIG® (miconazole ) , Highlights of Prescribing Information , Label ; Patient Information approved by the U . S . Food and Drug Administration ; Copyright 2012 Praelia Pharmaceuticals , Inc . , North (21 ) Appl.
    [Show full text]
  • ALBENDAZOLE (Extrapolation to All Ruminants)
    European Medicines Agency Veterinary Medicines and Inspections EMEA/MRL/865/03-FINAL June 2004 COMMITTEE FOR MEDICINAL PRODUCTS FOR VETERINARY USE ALBENDAZOLE (Extrapolation to all ruminants) SUMMARY REPORT (3) 1. Albendazole is a benzimidazole carbamate, used for the treatment of gastrointestinal infestations with roundworms, lungworms and tapeworms and adult flukes of Fasciola hepatica. Albendazole is currently entered into Annex I of Council Regulation (EEC) No. 2377/90 in accordance with the following table: Pharmacologically Marker residue Animal MRLs Target Other active substance(s) species tissues provisions Albendazole Sum of albendazole Bovine, 100 µg/kg Muscle sulphoxide, ovine 100 µg/kg Fat albendazole sulphone 1000 µg/kg Liver and albendazole 2- 500 µg/kg Kidney amino sulphone 100 µg/kg Milk expressed as albendazole 2. In reviewing the availability of endo- and ectoparasiticides for sheep and goats, albendazole was considered for extrapolation from bovine and ovine species to all ruminants. The considerations and criteria leading to the identification of albendazole are described in the Position Paper Regarding Availability of Veterinary Medicines – Extrapolation of MRLs (EMEA/CVMP/457/03-FINAL). 3. The scientific justification for this extrapolation was assessed in accordance with the Notes for Guidance on Risk Analysis Approach for Residues of Veterinary Medicinal Products in Food of Animal Origin (EMEA/CVMP/187/00-FINAL) and on the Establishment of Maximum Residue Limits for Minor Animal Species (EMEA/CVMP/153a/97-FINAL). 4. In setting the ADI in the original assessment of albendazole, the data summarised on the paragraphs below were considered. 5. The mode of action of albendazole is by binding strongly with the tubulin in the cells of nematodes.
    [Show full text]
  • Efficacy and Tolerability of Quinacrine Monotherapy and Albendazole Plus Chloroquine Combination Therapy in Nitroimidazole-Refractory Giardiasis: a Tropnet Study
    Klinik für Infektiologie & Spitalhygiene Efficacy and tolerability of quinacrine monotherapy and albendazole plus chloroquine combination therapy in nitroimidazole-refractory giardiasis: a TropNet study Andreas Neumayr, Mirjam Schunk, Caroline Theunissen, Marjan Van Esbroeck, Matthieu Mechain, Manuel Jesús Soriano Pérez, Kristine Mørch, Peter Sothmann, Esther Künzli, Camilla Rothe, Emmanuel Bottieau Journal Club 01.03.21 Andreas Neumayr Background on giardia treatment: • 1st-line treatment: 5-nitroimidazoles: metronidazole (1957), tinidazole, ornidazole, secnidazole • cure rate of 5NIs in 1st-line treatment: ~90% • in the last decade, an increase of 5NI-refractory giardia cases has been observed in travel medicine clinics across Europe: Hospital for Tropical Diseases, London: 2008: 15% --> 2013: 40% 70% of 5NI-refractory cases imported from India • 2nd-line treatment: effectiveness of a 2nd round with a 5NI: ~17% alternative drugs: albendazole, mebendazole, nitazoxanide, quinacrine, furazolidone, chloroquine, paromomycin 2012 TropNet member survey: 53 centres use 39 different treatment regimens, consisting of 7 different drugs in mono- or combination-therapy in various dosages and durations JC 01.03.21 Nabarro LE et al. Clin Microbiol Infect. 2015;21:791-6. • by 2013, there were only 13 reports of 2nd-line therapy for giardiasis (8 case series, 5 individual case reports): n=110 Cure rates Albendazole 6/32 18.7% Paromomycin 5/17 29.4% Nitazoxanide 2/5 40.0% Albendazole + 5-NI 42/53 79.2% Quinacrine 19/21 90.5% Quinacrine + 5-NI 14/14 100% Quinacrine + Paromomycin 2/2 100% • 2013: TropNet "GiardiaREF" study kick-off: Study on efficacy and tolerability of two 2nd-line regimens in nitroimidazole-refractory giardiasis: Quinacrine JC 01.03.21 Meltzer E et al.
    [Show full text]
  • Addyi Generic Name: Flibanserin Manufacturer
    Brand Name: Addyi Generic Name: Flibanserin Manufacturer: Sprout Pharmaceuticals Drug Class: Central Nervous System Agent, Serotonin Agonist, Dopamine antagonist Uses: Labeled Uses: Indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to: A co-existing medical or psychiatric condition, problems within the relationship, or the effects of a medication or other drug substance. Unlabeled Uses: none. Mechanism of Action: The mechanism of action for flibanserin in the treatment of hypoactive sexual desire disorder is unknown. Flibanserin has high affinity for serotonin (5-hydroxytryptamine or 5-HT) 1A receptors, as an agonist, and 5-HT2A receptors, as an antagonist, and moderate affinity for 5- HT2B, 5-HT2C, and dopamine D4 receptors as an antagonist Pharmacokinetics: Absorption: Tmax 0.75 hours Vd 50L t ½ 11 hours Clearance Not reported Protein binding 98% (albumin) Bioavailability 33% Metabolism: Flibanserin is extensively metabolized primarily by CYP3A4 and, to a lesser extent, CYP2C19 to at least 35 metabolites, with most of the metabolites occurring in low concentrations in plasma. Elimination: Flibanserin is primarily excreted through the kidneys in to urine (44%) and feces (51%). Two metabolites could be characterized that showed plasma concentration similar to that achieved with flibanserin: 6,21-dihydroxy-flibanserin-6,21-disulfate and 6- hydroxy-flibanserin-6-sulfate. These two metabolites are inactive. Efficacy: Katz M, DeRogatis LR, Ackerman R, et al. Efficacy of flibanserin in women with hypoactive sexual desire disorder: results from the BEGONIA trial. J Sex Med.
    [Show full text]
  • Study Assessing Prices, Availability and Affordability of Children's
    Study assessing prices, availability and affordability of children’s medicine in Chhattisgarh, India Part of the Better Medicine for Children project Authors Dr Antony KR Virendra Jain Puni Kokho Dr Kamlesh Jain The salient findings and views expressed in this report are solely those of the authors. Please direct correspondence to the authors: ([email protected], [email protected] [email protected], [email protected]). This publication does not necessarily represent the decisions or policies of the World Health Organization. ii Contents Acknowledgements ........................................................................................... v Abbreviations ................................................................................................... vi Executive summary ......................................................................................... vii Medicine availability .............................................................................................vii Medicine costs ................................................................................................... viii Affordability of standard treatment regimens ........................................................... ix Price components survey ...................................................................................... ix Conclusion .......................................................................................................... x 1. Introduction .................................................................................................
    [Show full text]
  • M2021: Pharmacogenetic Testing
    Pharmacogenetic Testing Policy Number: AHS – M2021 – Pharmacogenetic Prior Policy Name and Number, as applicable: Testing • M2021 – Cytochrome P450 Initial Presentation Date: 06/16/2021 Revision Date: N/A I. Policy Description Pharmacogenetics is defined as the study of variability in drug response due to heredity (Nebert, 1999). Cytochrome (CYP) P450 enzymes are a class of enzymes essential in the synthesis and breakdown metabolism of various molecules and chemicals. Found primarily in the liver, these enzymes are also essential for the metabolism of many medications. CYP P450 are essential to produce many biochemical building blocks, such as cholesterol, fatty acids, and bile acids. Additional cytochrome P450 are involved in the metabolism of drugs, carcinogens, and internal substances, such as toxins formed within cells. Mutations in CYP P450 genes can result in the inability to properly metabolize medications and other substances, leading to increased levels of toxic substances in the body. Approximately 58 CYP genes are in humans (Bains, 2013; Tantisira & Weiss, 2019). Thiopurine methyltransferase (TPMT) is an enzyme that methylates azathioprine, mercaptopurine and thioguanine into active thioguanine nucleotide metabolites. Azathioprine and mercaptopurine are used for treatment of nonmalignant immunologic disorders; mercaptopurine is used for treatment of lymphoid malignancies; and thioguanine is used for treatment of myeloid leukemias (Relling et al., 2011). Dihydropyrimidine dehydrogenase (DPD), encoded by the gene DPYD, is a rate-limiting enzyme responsible for fluoropyrimidine catabolism. The fluoropyrimidines (5-fluorouracil and capecitabine) are drugs used in the treatment of solid tumors, such as colorectal, breast, and aerodigestive tract tumors (Amstutz et al., 2018). A variety of cell surface proteins, such as antigen-presenting molecules and other proteins, are encoded by the human leukocyte antigen genes (HLAs).
    [Show full text]
  • Cleveland Clinic Laboratories
    Cleveland Clinic Laboratories Quantitative Urine Pain Management Drug Measurement with HPLC-MS/MS Background Information enzymatic hydrolysis is much milder, but needs longer incubation time to achieve sufficient (>80%) hydrolysis Pain management drugs are among the most prescribed efficiency.7 medications, and they are also the most abused class of prescription drugs.1-2 Therefore, many states including Ohio Cleveland Clinic Laboratories offer an HPLC-MS/MS method have enacted laws governing the prescription of pain for quantitative screening of 11 pain management drugs and management drugs. Patients enrolled in pain management five other commonly abused drugs in urine.8 In this method, programs need to be monitored for compliance, which total drug concentration is measured after enzymatic hydroly- means appropriate use of prescribed drugs and abstinence sis. This assay also includes an adulteration test using urine from non-prescribed drugs. test strips to ensure specimen quality. In addition to pain management, this test can also be used for monitoring Urine is the most commonly used specimen in monitoring patient compliance in rehabilitation programs. pain management and illicit drug use. A single urine specimen can be tested for a number of drugs. Immunoassay (IA) can The high sensitivity of this method is capable of detecting be used as a screening method, but it lacks specificity and drug manufacturing impurities. As an example, codeine is a sensitivity. For example, most immunoassay tests cannot known manufacturing impurity in morphine (~0.04%) and distinguish various opiate drugs and cannot detect oxymor- can be detected by this method.9 3-4 phone at all.
    [Show full text]
  • Individual Patient & Medication Factors That Invalidate Morphine
    Individual Patient & Medication Factors that Invalidate Morphine Milligram Equivalents Presented on June 7-8, 2021 at FDA Collaborative with various Federal Government Agency Stakeholders Jeffrey Fudin, PharmD, FCCP, FASHP, FFSMB Clinical Pharmacy Specialist & PGY2 Pain Residency Director Stratton VAMC, Albany NY Adjunct Associate Professor Albany College of Pharmacy & Health Sciences, Albany NY Western New England University College of Pharmacy, Springfield MA President, Remitigate Therapeutics, Delmar NY Disclosures Affiliation Role/Activities Abbott Laboratories Speaking, non-speakers bureau AcelRx Pharmaceuticals Acute perioperative pain (speakers bureau, consulting, advisory boards) BioDelivery Sciences International Collaborative publications, consulting, advisory boards Firstox Laboratories Micro serum testing for substances of abuse (consulting) GlaxoSmithKline (GSK) Collaborative non-paid poster presentations) Hisamitsu America Inc Advisory Board Hikma Pharmaceuticals Advisory Board Scilex Pharmaceuticals Collaborative non-paid publications Salix Pharmaceuticals Speakers bureau, consultant, advisory boards Torrent Pharmaceuticals Lecture, non-speakers bureau Learning Objectives At the completion of this activity, participants will be able to: 1. Explain opioid conversion and calculation strategies when developing a care plan for patients with chronic pain. 2. Assess patient-specific factors that warrant adjustment to an opioid regimen. 3. Identify important drug interactions that can affect opioid serum levels. 4. Describe how pharmacogenetic differences can affect opioid efficacy, toxicity, and tolerability. Not All Opioids are Created Equally Issues with MEDD & Opioid Conversion1-4 › Pharmacogenetic variability › Drug interactions › Lack of universal morphine equivalence › Specific opioids that should never have an MEDD – Methadone, Buprenorphine, Tapentadol, Tramadol 1. Fudin J, Marcoux MD, Fudin JA. Mathematical Model For Methadone Conversion Examined. Practical Pain Management. Sept. 2012. 46-51. 2. Donner B, et al.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8.492,564 B2 Beguin Et Al
    USOO8492.564B2 (12) United States Patent (10) Patent No.: US 8.492,564 B2 Beguin et al. (45) Date of Patent: Jul. 23, 2013 (54) SALVINORIN DERIVATIVES AND USES Béguin et al., “Differential signaling properties at the kappa opioid THEREOF receptor of 12-epi-Salvinorin A and its analogues. Bioorg Med Chem Lett. 22: 1023-1026, 2012. (75) Inventors: Cecile Beguin, Lexington, MA (US); Béguin et al., “Modification of the furan ring of salvinorin A: iden Justin Stephen Potuzak, Millis, MA tification of a selective partial agonist at the kappa opioid receptor.” 17: 1370-1380, Epub Dec. 14, 2008. (US); Thomas Anthony Munro, Béguinet al., "N-Methylacetamide Analog of Salvinorin A: A Highly Cambridge, MA (US); Katharine K. Potent and Selective K-Opioid Receptor Agonist with Oral Efficacy.” Duncan, San Diego, CA (US); William J. Pharmacol. Exp. Ther, 324; 188-195 (2008). A. Carlezon, Lincoln, MA (US); Bruce Béguin et al., “Synthesis and In Vitro Evaluation of Salvinorin A M. Cohen, Lexington, MA (US); Analogues: Effect of Configuration at C(2) and Substitution at Lee-yuan Liu-Chen, Media, PA (US) C(18).” Bioorg. Med. Chem. Lett. 16:4679-4685 (2006). Béguin et al., “Synthesis and InVitro Pharmacological Evaluation of (73) Assignees: The McLean Hospital Corporation, Salvinorin A Analogues Modified at C(2).” Bioorg. Med. Chem. Lett. Belmont, MA (US); Temple University 15:2761-2765 (2005). School of Medicine, Philadelphia, PA Bigham et al., “Divinatorins A-C, New Neoclerodane Diterpenoids from the Controlled SageSalvia divinorum,'.J. Nat. Prod 66: 1242 (US) 1244 (2003). Bikbulatov et al., “Short synthesis of a novel class of salvinorin A (*) Notice: Subject to any disclaimer, the term of this analogs with hemiacetalic structure.” Tetrahedron Lett.
    [Show full text]
  • ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update
    The ASAM NATIONAL The ASAM National Practice Guideline 2020 Focused Update Guideline 2020 Focused National Practice The ASAM PRACTICE GUIDELINE For the Treatment of Opioid Use Disorder 2020 Focused Update Adopted by the ASAM Board of Directors December 18, 2019. © Copyright 2020. American Society of Addiction Medicine, Inc. All rights reserved. Permission to make digital or hard copies of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for commercial, advertising or promotional purposes, and that copies bear this notice and the full citation on the fi rst page. Republication, systematic reproduction, posting in electronic form on servers, redistribution to lists, or other uses of this material, require prior specifi c written permission or license from the Society. American Society of Addiction Medicine 11400 Rockville Pike, Suite 200 Rockville, MD 20852 Phone: (301) 656-3920 Fax (301) 656-3815 E-mail: [email protected] www.asam.org CLINICAL PRACTICE GUIDELINE The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update 2020 Focused Update Guideline Committee members Kyle Kampman, MD, Chair (alpha order): Daniel Langleben, MD Chinazo Cunningham, MD, MS, FASAM Ben Nordstrom, MD, PhD Mark J. Edlund, MD, PhD David Oslin, MD Marc Fishman, MD, DFASAM George Woody, MD Adam J. Gordon, MD, MPH, FACP, DFASAM Tricia Wright, MD, MS Hendre´e E. Jones, PhD Stephen Wyatt, DO Kyle M. Kampman, MD, FASAM, Chair 2015 ASAM Quality Improvement Council (alpha order): Daniel Langleben, MD John Femino, MD, FASAM Marjorie Meyer, MD Margaret Jarvis, MD, FASAM, Chair Sandra Springer, MD, FASAM Margaret Kotz, DO, FASAM George Woody, MD Sandrine Pirard, MD, MPH, PhD Tricia E.
    [Show full text]
  • (Flibanserin) (Flibanserin) Tablets
    ™ MEDICATION GUIDE addyi ADDYI™ (add-ee) (flibanserin) (flibanserin) Tablets Read this Medication Guide before you start taking ADDYI™ and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor. What is the most important information I should know about ADDYI? Your risk of severe low blood pressure and fainting (loss of consciousness) is increased if you take ADDYI and: • drink alcohol. Do not drink alcohol if you take ADDYI. • take certain prescription medicines, over-the-counter medicines, or herbal supplements. Do not take or start taking any prescription medicines, over-the-counter medicines, or herbal supplements while taking ADDYI until you have talked with your doctor. Your doctor will tell you if it is safe to take other medicines or herbal supplements while you are taking ADDYI. • have liver problems. Do not take ADDYI if you have liver problems. If you take ADDYI and you feel lightheaded or dizzy, lie down right away. Get emergency medical help or ask someone to get emergency medical help for you if the symptoms do not go away or if you faint (lose consciousness). If you faint (lose consciousness), tell your doctor as soon as you can. ADDYI is only available through the ADDYI Risk Evaluation and Mitigation Strategy (REMS) Program because of the increased risk of severe low blood pressure and fainting (loss of consciousness) with alcohol use. You can only get ADDYI from pharmacies that are enrolled in the ADDYI REMS Program. For more information about the Program and a list of pharmacies that are enrolled in the ADDYI REMS Program, go to www.AddyiREMS.com or call 1-844-PINK-PILL (1-844- 746-5745).
    [Show full text]