# Evaluating the antagonist effect of naltrexone implant via opioid challenge tests with escalating doses of hydromorphone injection in former heroin dependent patients

## TL;DR

A naltrexone implant effectively blocks opioid effects in former heroin users, with higher doses providing stronger and longer-lasting results.

## Contribution

This study evaluates the effectiveness and safety of a long-acting naltrexone implant in blocking opioid effects in former heroin users.

## Key findings

- Naltrexone implant showed significant antagonistic effects during hydromorphone challenge tests.
- Higher doses of naltrexone implant provided stronger and longer-lasting opioid blockade.
- Pharmacokinetic data showed effective plasma concentrations lasting over 148 days.

## Abstract

Opioid dependence is a serious, life-threatening condition with severe social impacts. Naltrexone (NTX) can weaken the effect of opioids and effectively reduce opioid self-administration, discrimination, and opioid-induced subjective effects, and the oral dosage form has been approved for the treatment of opioid dependence. However, the effectiveness of oral naltrexone as an opioid antagonist has been limited due to poor patient adherence. A long-acting formulation in the form of naltrexone implant (NTX-IMP) with a five-month duration of action may address this issue and improve outcomes. This study (trial registration number: CTR20181954) aimed to evaluate the effect, safety, and pharmacokinetics of NTX-IMP in agonist effects via hydromorphone challenge test, and to determine optimal dosages for future research. Thirty-one former opioid-dependent individuals were randomized to the 0.9g or the 1.5g NTX-IMP group. All subjects exhibited significant antagonistic effects during hydromorphone challenge test. Calculation of slope between VAS score or pupil diameter and hydromorphone dose suggested a stronger antagonistic effect in the 1.5 g group. Pharmacokinetic data suggested that effective plasma naltrexone concentration (≥1ng/ml) was detected from the third day for over 148 days, with higher concentration and longer duration in the 1.5 g group. All subjects tolerated NTX-IMP well. The findings indicate that the NXT-IMP effectively blocks the agonistic effects of hydromorphone in a dose-dependent manner.