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Yee D.A.,University of California at San Diego | Best B.M.,University of California at San Diego | Atayee R.S.,University of California at San Diego | Pesce A.J.,Millennium Laboratories | Pesce A.J.,University of California at San Diego
Journal of Analytical Toxicology | Year: 2012

The object of this study was to evaluate the metabolism of oxycodone to oxymorphone in a pain patient population using a quantitative liquid chromatography-tandem mass spectrometry analysis of 32,656 urine specimens obtained from pain patients between March 2008 and Feb 2010. The observed excretion was modeled using logarithmic transformation and approximated a Gaussian distribution. Oxycodone excretion into urine had a geometric mean of 1.93 mg/g of creatinine and oxymorphone had a value of 0.41 mg/g of creatinine. Increasing concentrations of oxycodone correlated with a smaller proportion of oxymorphone excretion suggesting saturation of oxycodone metabolism. Urine samples containing oxycodone without oxymorphone allowed an estimation of the proportion of poor metabolizers (2.4±2.1%) in the population. A similar analysis of samples containing oxymorphone without oxycodone gave an estimate of the proportion of ultra-rapid metabolizers (1.8±1.1%) in the population. Samples with concentrations of oxycodone above 10 mg/g of creatinine showed a sub-population of subjects with metabolic ratios roughly 100-fold less than the linear predictive model in this study. This study describes typical ranges for oxycodone and oxymorphone in urine, and showed that it is possible to identify fast or slow metabolizers who may be at risk for adverse events. © The Author [2012]. Published by Oxford University Press. All rights reserved.


Passik S.D.,Millennium Laboratories | Webster L.,CRI Lifetree Research
Journal of opioid management | Year: 2014

Prescription opioid analgesics with a wide range of potencies are currently used for the treatment of chronic pain. Yet understanding the clinical relevance and therapeutic consequences of opioid potency remains ill defined. Both patients and clinicians alike have misperceptions about opioid potency, expecting that less-potent opioids will be less effective or fearing that more-potent opioids are more dangerous or more likely to be abused. In this review, common myths about the potency of opioid analgesics will be discussed. Clinicians should understand that pharmacologic potency per se does not necessarily imply more effective analgesia or higher abuse liability. Published dose conversion tables may not accurately calculate the dose for effective and safe rotation from one opioid to another in patients receiving long-term opioid therapy because they are based on limited data that may not apply to chronic pain. Differences in pharmacologic potency are largely accounted for by the actual doses prescribed, according to individualized patient need. Factors for achieving effective analgesia and reducing the risks involved with opioid use include careful medication selection based on patient characteristics, appropriate dosing titration and opioid rotation practices, knowledge of product formulation characteristics (eg, extended release, immediate release, and tamper-resistant features), and an awareness of differences in opioid pharmacokinetics and metabolism. Clinicians should remain vigilant in monitoring patients on any opioid medication, regardless of classification along the opioid potency continuum.


Cole J.M.,University of California at San Diego | Best B.M.,University of California at San Diego | Pesce A.J.,Millennium Laboratories | Pesce A.J.,University of California at San Diego
Journal of Opioid Management | Year: 2010

Background: The rising popularity of the fentanyl transdermal patch and the striking number of deaths attributed to its prescribed use have brought attention to the large variability of fentanyl metabolism and the need for predictive models to prevent toxicity. Objective: The purpose of this study was to determine the amount of both intra-subject and intersubject variability in fentanyl metabolism and excretion, using urinary excretion data from patients with chronic pain prescribed the fentanyl transdermal patch. Methods: Liquid chromatography tandem mass spectrometry analytical technique was used to quantitate fentanyl and norfentanyl concentrations in spot urine specimens, after incubation with glucuronidase. Descriptive statistics and graphical analysis were conducted using Microsoft Excel 2007. Analysis was conducted on 206 subjects with ≥2 visits listing transdermal fentanyl as current medication. Outliers and subjects with no detectable levels of drug were excluded, resulting in subject populations of 200 (all subjects analyzed) and 166 (subjects with drug concentrations above the instrument detection limit for all visits). Results: The geometric mean metabolic ratio (MR) of norfentanyl to fentanyl was 6.2 X ÷ 2.4. A wide distribution was observed in total fentanyl load (1,000-fold) and MR (200-fold). The intersubject geometric standard deviation in MR was 2.4 (95% confidence interval [CI] for MR: 1-37) and the intrasubject geometric standard deviation was 1.8 (95% CI for MR: 2-20). Conclusion: The level of intrasubject variability over time in the pharmacokinetics of the fentanyl patch is much greater than previously observed and may be due to variability in absorption, interference of metabolism by concomitant medications, and variable metabolism due to genetic polymorphisms. The variation in the MR between subjects and within subjects may explain the unpredictable adverse effects observed with use of transdermal fentanyl. © 2010 Journal of Opioid Management, All Rights Reserved.


Gordon A.,Wasser Pain Management Center | DePriest A.Z.,Aegis USA | Axford-Gatley R.A.,MedSolutions | Passik S.D.,Millennium Laboratories
Postgraduate Medicine | Year: 2014

The use of opioids for patients with chronic noncancer pain has increased dramatically, and with increasing use there is increasing concern about the potential for abuse and addiction during long-term treatment. Clinicians should avoid viewing formal or subjective risk assessment as a means of classifying patients into 2 distinct categories: compliant patients and substance abusers. The provider who perceives a patient as compliant may have a complacent attitude toward aberrant drug-related behavior, presuming that these signs reflect inadequately controlled pain, to be addressed by dose escalation. The provider who perceives a patient as a substance abuser may refuse to provide treatment for pain, leaving the patient to seek either illicit drugs or prescribed treatment from another provider. In fact, in seemingly compliant patients, any noncompliant use of opioids presents a safety risk regardless of the explanations offered. Even in known or suspected drug abusers, chronic pain warrants the use of adequate pharmacotherapy, although treatment in such cases may exclude drugs with high abuse potential. Thus, all aberrant drug-related behavior should be addressed within a treatment plan that combines adequate pain care with suitable interventions for the aberrant behavior, following current best practice strategies. This approach is consistent with the approach taken with other health conditions, such as diabetes or hypertension, for which it is understood that noncompliance with therapy presents a risk of harm. © Postgraduate Medicine.


Passik S.D.,Millennium Laboratories
Advances in Therapy | Year: 2014

Introduction: Pain - including acute or persistent acute pain - is a common condition that is increasingly being treated with opioids in the United States. The acute pain treatment setting may represent a key target for addressing the growing epidemic of prescription drug abuse occurring hand in hand with the rise in opioid prescribing. Balancing the needs of pain treatment with abuse prevention can be challenging for clinicians. Methods: This article identified efforts to balance opioid abuse risks with opioid availability through the extensive experience of the author in this field. In addition, PubMed literature searches using terms such as "prescription opioid abuse", "abuse-deterrent opioids", and "tamper-resistant opioids"; and inspection of the bibliographies of relevant articles were used to identify relevant sources. Results: These multifaceted efforts have included: improving assessment of patient risk for drug misuse, abuse, or diversion; funding of and encouraging referral to addiction treatment programs; access to and widespread use of prescription monitoring programs (PMPs); public knowledge of prescription opioid abuse; proper storage of opioid medications; and development of new formulations designed to resist tampering and deter abuse. This review discusses the problem of prescription opioid abuse and strategies to minimize risk within the context of acute pain treatment, and explores the potential role of tamper-resistant opioid formulations and other abuse deterrence strategies in the area of acute or persistent acute pain management. Conclusion: In order to stem the tide of prescription opioid abuse and preserve the availability of opioids as a much needed analgesic option, a multifaceted approach that includes tamper-resistant opioid formulations - for chronic or acute pain - along with strategies such as improved patient risk assessment, funding for and referral to addiction treatment programs, greater use of PMPs, and raised awareness of prescription opioid abuse is needed. © 2014 Springer Healthcare.

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