Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Clinical Drug Investigation
Published in: Clinical Drug Investigation 2/2020

01-02-2020 | Naltrexone | Original Research Article

Pharmacokinetics and Bioequivalence Evaluation of a New Oxycodone Tamper-Resistant Tablet Administered with an Opioid Antagonist in Patients with Chronic Pain

Authors: Zhu Luo, Jia Miao, Shiqing Shu, Ying Wang, Xiaohong Zhu, Chao Hu, Yali Shen

Published in: Clinical Drug Investigation | Issue 2/2020

Login to get access

Abstract

Background and Objectives

Oxycodone tamper resistant (OTR) is a new extended-release abuse-deterrent formulation providing improvements in the tamper resistant characteristics. This study aimed to investigate the pharmacokinetic properties of the new OTR tablets and evaluate the bioequivalence of oxycodone from OTR and the original extended release (ER) formulation tablets administered with an opioid antagonist in patients with chronic pain.

Methods

In this open-label, randomized, cross-over study, the enrolled patients were randomised to receive a single dose of 40 mg OTR or 40 mg OXYCONTIN® (OXY) tablet administered with naltrexone blockade under fasting conditions. Serial blood samples for pharmacokinetic analysis were collected. Plasma oxycodone was quantified by a high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method. Tolerability was evaluated by monitoring adverse events, physical examinations, 12-lead ECG and laboratory tests.

Results

A total of 38 patients were enrolled and 33 subjects completed the study. After a single dose of 40 mg tablets, pharmacokinetic results of the new OTR tablet were found to be similar to those of original extended-release oxycodone tablet. OTR 40 mg was bioequivalent to OXY 40 mg and was well tolerated in patients with chronic pain.

Conclusions

The new OTR formulation could provide a new choice in the treatment of chronic pain and reduce the potential for oxycodone abuse.
Chictr.org identifier: ChiCTR1800017253.
Appendix
Available only for authorised users
Literature
1.
Riley J, Eisenberg E, Muller-Schwefe G, et al. Oxycodone: a review of its use in the management of pain. Curr Med Res Opin. 2008;24(1):175–92.CrossRef
2.
Lugo RA, Kern SE. The pharmacokinetics of oxycodone. J Pain Palliat Care Pharmacother. 2005;18(4):17–30.CrossRef
3.
The Medical Letter Inc. Abuse-deterrent opioids. Med Lett Drugs Ther. 2017;59(1522):95–6.
4.
Pergolizzi JV Jr, Raffa RB, Taylor R Jr, et al. Abuse-deterrent opioids: an update on current approaches and considerations. Curr Med Res Opin. 2018;34(4):711–23.CrossRef
5.
Keast SL, Owora A, Nesser N, et al. Evaluation of abuse-deterrent or tamper-resistant opioid formulations on overall health care expenditures in a state medicaid program. J Manag Care Spec Pharm. 2016;22(4):347–56.PubMed
6.
Guy GP Jr, Zhang K, Bohm MK, et al. Vital signs: changes in opioid prescribing in the United States, 2006–2015. MMWR Morb Mortal Wkly Rep. 2017;66(26):697–704.CrossRef
7.
Nguyen V, Raffa RB, Taylor R, et al. The role of abuse-deterrent formulations in countering opioid misuse and abuse. J Clin Pharm Ther. 2015;40(6):629–34.CrossRef
8.
Investigator’s Brochure of Oxycodone Tamper Resistant (Reformulated Oxycontin), Purdue Pharma, released date Jun/2016, edition number 16.1.
9.
Shen Y, Luo Z, Yu Q, et al. Pharmacokinetics of dimemorfan phosphate tablets in healthy Chinese volunteers. Eur J Clin Pharmacol. 2017;73(6):709–15.CrossRef
10.
11.
12.
U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research. Abusedeterrent opioids—evaluation and labeling: guidance for industry. Silver Spring: US DoH; 2015.
13.
OxyContin (oxycodone hydrochloride) extended-release tablets [package insert]. Stamford (CT): Purdue Pharma L.P.; 2016.
14.
Poyhia R, Seppala T, Olkkola KT, et al. The pharmacokinetics and metabolism of oxycodone after intramuscular and oral administration to healthy subjects. Br J Clin Pharmacol. 1992;33(6):617–21.CrossRef
15.
Mandema JW, Kaiko RF, Oshlack B, Reder RF, Stanski DR. Characterization and validation of a pharmacokinetic model for controlled-release oxycodone. Br J Clin Pharmacol. 1996;42(6):747–56.CrossRef
16.
Kokki M, Välitalo P, Rasanen I, Aaltomaa S, Ojanperä I, Eskelinen M, et al. Absorption of different oral dosage forms of oxycodone in the elderly: a cross-over clinical trial in patients undergoing cystoscopy. Eur J Clin Pharmacol. 2012;68(10):1357–63.CrossRef
17.
Kinnunen M, Piirainen P, Kokki H, et al. Updated clinical pharmacokinetics and pharmacodynamics of oxycodone. Clin Pharmacokinet. 2019;58(6):705–25.CrossRef
18.
Pöyhiä R, Vainio A, Kalso E. A review of oxycodone’s clinical pharmacokinetics and pharmacodynamics. J Pain Symptom Manag. 1993;8(2):63–7.CrossRef
19.
Chen ZR, Irvine RJ, Somogyi AA, et al. Mu receptor binding of some commonly used opioids and their metabolites. Life Sci. 1991;48(22):2165–71.CrossRef
20.
Alexander SPH, Mathie A, Peters JA. Guide to receptors and channels (GRAC), 4th edn. Br J Pharmacol. 2009;158(Suppl. 1):S1–25.
21.
Kokki H, Kokki M. Central nervous system penetration of the opioid oxycodone. In: Preedy VR, editor. Neuropathology of drug addictions and substance misuse, vol. 3. 1st ed. New York: Academic; 2016 (ISBN 9780128006344).CrossRef
22.
Bostrom E, Hammarlund-Udenaes M, Simonsson US. Blood–brain barrier transport helps to explain discrepancies in in vivo potency between oxycodone and morphine. Anesthesiology. 2008;108(3):495–505.CrossRef
23.
Bostrom E, Simonsson US, Hammarlund-Udenaes M. In vivo blood–brain barrier transport of oxycodone in the rat: indications for active influx and implications for pharmacokinetics/pharmacodynamics. Drug Metab Dispos. 2006;34(9):1624–31.CrossRef
24.
Lemberg KK, Siiskonen AO, Kontinen VK, et al. Pharmacological characterization of noroxymorphone as a new opioid for spinal analgesia. Anesth Analg. 2008;106(2):463–70 (table of contents).CrossRef
25.
Kokki M, Valitalo P, Kuusisto M, et al. Central nervous system penetration of oxycodone after intravenous and epidural administration. Br J Anaesth. 2014;112(1):133–40.CrossRef
26.
Sadiq MW, Bostrom E, Keizer R, et al. Oxymorphone active uptake at the blood–brain barrier and population modeling of its pharmacokinetic–pharmacodynamic relationship. J Pharm Sci. 2013;102(9):3320–31.CrossRef
27.
Vadivelu N, Chang D, Helander EM, et al. Ketorolac, oxymorphone, tapentadol, and tramadol: a comprehensive review. Anesthesiol Clin. 2017;35(2):e1–20.CrossRef
28.
Klimas R, Witticke D, El Fallah S, et al. Contribution of oxycodone and its metabolites to the overall analgesic effect after oxycodone administration. Expert Opin Drug Metab Toxicol. 2013;9(5):517–28.CrossRef
29.
Lalovic B, Kharasch E, Hoffer C, et al. Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: role of circulating active metabolites. Clin Pharmacol Ther. 2006;79(5):461–79.CrossRef
30.
Samer CF, Daali Y, Wagner M, et al. The effects of CYP2D6 and CYP3A activities on the pharmacokinetics of immediate release oxycodone. Br J Pharmacol. 2010;160(4):907–18.CrossRef
31.
Samer CF, Daali Y, Wagner M, et al. Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety. Br J Pharmacol. 2010;160(4):919–30.CrossRef
32.
Zwisler ST, Enggaard TP, Noehr-Jensen L, et al. The hypoalgesic effect of oxycodone in human experimental pain models in relation to the CYP2D6 oxidation polymorphism. Basic Clin Pharmacol Toxicol. 2009;104(4):335–44.CrossRef
33.
Zwisler ST, Enggaard TP, Mikkelsen S, et al. Impact of the CYP2D6 genotype on post-operative intravenous oxycodone analgesia. Acta Anaesthesiol Scand. 2010;54(2):232–40.CrossRef
34.
Stamer UM, Zhang L, Book M, et al. CYP2D6 genotype dependent oxycodone metabolism in postoperative patients. PLoS One. 2013;8(3):e60239.CrossRef
35.
Gudin J, Levy-Cooperman N, Kopecky EA, et al. Comparing the effect of tampering on the oral pharmacokinetic profiles of two extended-release oxycodone formulations with abuse-deterrent properties. Pain Med. 2015;16(11):2142–51.CrossRef
36.
Webster LR, Bath B, Medve RA, et al. Randomized, double-blind, placebo-controlled study of the abuse potential of different formulations of oral oxycodone. Pain Med. 2012;13(6):790–801.CrossRef
37.
Franke RM, Morton T, Devarakonda K. Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets. Drug Des Dev Ther. 2015;9:4587–97.
38.
Liukas A, Kuusniemi K, Aantaa R, et al. Elimination of intravenous oxycodone in the elderly: a pharmacokinetic study in postoperative orthopaedic patients of different age groups. Drugs Aging. 2011;28(1):41–50.CrossRef
39.
Morton T, Franke R, Devarakonda K. Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following multiple oral doses of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets. Pain Pract. 2016;16(6):730–6.CrossRef
40.
Andreassen TN, Klepstad P, Davies A, et al. Influences on the pharmacokinetics of oxycodone: a multicentre cross-sectional study in 439 adult cancer patients. Eur J Clin Pharmacol. 2011;67(5):493–506.CrossRef
41.
Elder NM, Atayee RS, Best BM, et al. Observations of urinary oxycodone and metabolite distributions in pain patients. J Anal Toxicol. 2014;38(3):129–34.CrossRef
42.
Davis MP. Pharmacokinetic and pharmacodynamic evaluation of oxycodone and naltrexone for the treatment of chronic lower back pain. Expert Opin Drug Metab Toxicol. 2016;12(7):823–31.CrossRef
43.
Pergolizzi JV Jr, Taylor R Jr, LeQuang JA, et al. Managing severe pain and abuse potential: the potential impact of a new abuse-deterrent formulation oxycodone/naltrexone extended-release product. J Pain Res. 2018;11:301–11.CrossRef
44.
Chindalore VL, Craven RA, Yu KP, et al. Adding ultralow-dose naltrexone to oxycodone enhances and prolongs analgesia: a randomized, controlled trial of Oxytrex. J Pain. 2005;6(6):392–9.CrossRef
Metadata
Title
Pharmacokinetics and Bioequivalence Evaluation of a New Oxycodone Tamper-Resistant Tablet Administered with an Opioid Antagonist in Patients with Chronic Pain
Authors
Zhu Luo
Jia Miao
Shiqing Shu
Ying Wang
Xiaohong Zhu
Chao Hu
Yali Shen
Publication date
01-02-2020
Publisher
Springer International Publishing
Published in
Clinical Drug Investigation / Issue 2/2020
Print ISSN: 1173-2563
Electronic ISSN: 1179-1918
DOI
https://doi.org/10.1007/s40261-019-00870-w

Other articles of this Issue 2/2020

Clinical Drug Investigation 2/2020 Go to the issue

Original Research Article

Early and Late Switch from Ranibizumab to an Intravitreal Dexamethasone Implant in Patients with Diabetic Macular Edema in the Event of a Poor Anatomical Response

Original Research Article

PCSK9 Inhibitors’ New Users: Analysis of Prescription Patterns and Patients’ Characteristics from an Italian Real-world Study

Original Research Article

A Caprini Risk Score-Based Cost-Effectiveness Analysis of Enoxaparin for the Thromboprophylaxis of Patients After Nonorthopedic Surgery in a Chinese Healthcare Setting

Original Research Article

Safety, Tolerability, and Effects of Sodium Bicarbonate Inhalation in Cystic Fibrosis

Original Research Article

Cost Effectiveness of Ceritinib and Alectinib Versus Crizotinib in First-Line Anaplastic Lymphoma Kinase-Positive Advanced Non-small-cell Lung Cancer

Short Communication

Bleeding Risk of Therapeutic Unfractionated Heparin and Low Molecular Weight Heparin in Patients with Cirrhosis