Abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered crushed oxycodone HCl abuse‐deterrent controlled‐release tablets in recreational opioid users

Abstract

The objective of this study was to evaluate abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered, crushed reformulated OxyContin® (oxycodone HCl controlled-release) tablets (ORF), relative to crushed original OxyContin® (OC), oxycodone powder (Oxy API), and OC placebo. This randomized, double-blind, positive- and placebo-controlled crossover study enrolled healthy, adult, nonphysically dependent recreational opioid users with recent history of intranasal drug abuse (N = 27). Active treatments contained oxycodone (30 mg). Pharmacokinetics, pharmacodynamics (e.g., Overall Drug Liking [ODL], Take Drug Again [TDA], and High Visual Analog Scales [VAS]; Subjective Drug Value [SDV]; pupillometry; intranasal irritation), and safety (e.g., adverse events, vital signs, laboratory tests) were assessed to 24 hours postdose. Crushed ORF administration yielded reduced oxycodone Cmax and increased Tmax versus crushed OC and Oxy API. Peak effects for pharmacodynamic measures were delayed with ORF (1–2 hours) versus OC and Oxy API (0.5–1 hour). ODL, TDA, High VAS, and SDV Emax values were significantly lower (P ≤ .05) and some intranasal irritation ratings were greater for ORF versus OC and Oxy API. No significant or unexpected safety findings were observed. Compared with OC and Oxy API, intranasally administered ORF was associated with lower and delayed peak plasma concentrations, decreased drug-liking, and decreased intranasal tolerability. This suggests that ORF has a decreased potential for intranasal oxycodone abuse. There were no significant or unexpected safety findings. As is true for all abuse potential studies, epidemiological or other appropriate post-marketing studies are required to assess the impact of the reduction in intranasal oxycodone abuse potential observed in the present study on real-world patterns of ORF misuse, abuse, and diversion.

Opioid Dose- and Route-Dependent Efficacy of Oxycodone and Heroin Vaccines in Rats

“…In a clinical laboratory study of nondependent opioid users, 20 mg (0.29 mg/kg) oxycodone administered intravenously (Backonja et al, 2016) or 30 mg (0.43 mg/kg) administered as intranasal powder (Harris et al, 2014) produced significant drug-liking effects. These doses are at the lower end of the range administered to rats intravenously in the current study.…”

Routes of abuse of prescription opioid analgesics: a review and assessment of the potential impact of abuse-deterrent formulations

“…Studies have shown that it is less attractive to recreational drug abusers than the original extended-release formulation. [101,102] Targiniq™ ER (Purdue Pharma LP) was approved in the USA in July 2014. This abuse-deterrent formulation contains oxycodone combined with naloxone -an antagonist that blocks the euphoric effects of oxycodone if the tablet is crushed for snorting or manipulated for injection.…”

How Resistant to Tampering are Codeine Containing Analgesics on the Market? Assessing the Potential for Opioid Extraction

“…Tampering of codeine is no exception [46–48]. Still published research findings of assessments of harm, medicine misuse, and tampering will in some cases provide an additional outlet for tampering, offering insights into types of opioids tampered with, specific methods and tools used for tampering, how well formulations can be tampered with, and uptake of tampering solutions by the body [41, 42, 44, 49, 50]. It will come as no surprise to researchers frequenting drug discussion forums that published data are cited amongst users as evidence of which drugs (or way of using drugs) gives the desired effects.…”