Pharmacokinetic and pharmacodynamic considerations in developing a response to the opioid epidemic

ABSTRACT

Introduction: Opioids continue to be used widely for pain management. Widespread availability of prescription opioids has led to opioid abuse and addiction. Besides steps to reduce inappropriate prescribing, exploiting opioid pharmacology to make their use safer is important.

Areas covered: This article discusses the pathology and factors underlying opioid abuse. Pharmacokinetic and pharmacodynamic properties affecting abuse liability of commonly abused opioids have been highlighted. These properties inform the development of ideal abuse deterrent products. Mechanisms and cost-effectiveness of available abuse deterrent products have been reviewed in addition to the pharmacology of medications used to treat addiction.

Expert opinion: The opioid crisis presents unique challenges to managing pain effectively given the limited repertoire of strong analgesics. The 5-point strategy to combat the opioid crisis calls for better preventive, treatment, and recovery services, better data, better pain management, better availability of overdose-reversing drugs and better research. There is an urgent need to decrease the cost of abuse deterrent opioids which deters their cost-effectiveness. In addition, discovery of novel analgesics, further insight into central and peripheral pain mechanisms, understanding genomic risk profiles for efficient targeted efforts, and education will be key to winning this fight against the opioid crisis.

KEYWORDS:

• Opioid crisis
• pk-PD
• abuse deterrent product
• pain pharmacology

Article highlights

• Opioid abuse is a multifactorial disorder that is associated with disrupted sub-cortical reward circuits and decision-making abilities.

• This review characterizes the PK-PD of opioids commonly used in abuse, and describes implications for abuse liability and development of opioid abuse deterrent formulations.

• Parameters such as drug physicochemical properties, C_max, T_max, rate/route of administration, absorption rate, receptor affinity, on-off kinetics and development of tolerance to opioid effects play a role in abuse liability.

• There are six mechanisms that have been exploited to develop abuse deterrent opioids. However, these strategies are currently not cost-effective.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Time for research and preparation of the manuscript was supported by departmental salaries and postdoctoral research support for Dr. Hahn [PI: Chidambaran, 1R01AR075857-01].