Evaluating the antagonist effect of naltrexone implant via opioid challenge tests with escalating doses of hydromorphone injection in former heroin dependent patients
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 treatm...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Psychiatry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1441598/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832582029062963200 |
|---|---|
| author | Wei Qu Xuyi Wang Chongyang Dong Tao Zhang Shugui Yin Zhijun Sun Shiqiang Wang Anni Guo Wei Hao |
| author_facet | Wei Qu Xuyi Wang Chongyang Dong Tao Zhang Shugui Yin Zhijun Sun Shiqiang Wang Anni Guo Wei Hao |
| author_sort | Wei Qu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6713deec49f54bfbacb8e00fa6db9dfe |
| institution | Kabale University |
| issn | 1664-0640 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj-art-6713deec49f54bfbacb8e00fa6db9dfe2025-01-30T06:22:33ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402025-01-011610.3389/fpsyt.2025.14415981441598Evaluating the antagonist effect of naltrexone implant via opioid challenge tests with escalating doses of hydromorphone injection in former heroin dependent patientsWei Qu0Xuyi Wang1Chongyang Dong2Tao Zhang3Shugui Yin4Zhijun Sun5Shiqiang Wang6Anni Guo7Wei Hao8Research Department, Shenzhen Sciencare Pharmaceutical Co., Ltd., Shenzhen, ChinaInstitute of Mental Health of the Second Xiangya Hospital of Central South University, National Medical Center for Mental Disorders, Changsha, ChinaPeking University Clinical Research Institute, Peking University First Hospital, Beijing, ChinaResearch Department, Shenzhen Sciencare Pharmaceutical Co., Ltd., Shenzhen, ChinaResearch Department, Shenzhen Sciencare Pharmaceutical Co., Ltd., Shenzhen, ChinaResearch Department, Shenzhen Sciencare Pharmaceutical Co., Ltd., Shenzhen, ChinaResearch Department, Shenzhen Sciencare Pharmaceutical Co., Ltd., Shenzhen, ChinaResearch Department, Shenzhen Sciencare Pharmaceutical Co., Ltd., Shenzhen, ChinaInstitute of Mental Health of the Second Xiangya Hospital of Central South University, National Medical Center for Mental Disorders, Changsha, ChinaOpioid 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.https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1441598/fullnaltrexoneopioid blockageopioid challengehydromorphonelong-acting naltrexone implant (NTX-IMP) |
| spellingShingle | Wei Qu Xuyi Wang Chongyang Dong Tao Zhang Shugui Yin Zhijun Sun Shiqiang Wang Anni Guo Wei Hao Evaluating the antagonist effect of naltrexone implant via opioid challenge tests with escalating doses of hydromorphone injection in former heroin dependent patients Frontiers in Psychiatry naltrexone opioid blockage opioid challenge hydromorphone long-acting naltrexone implant (NTX-IMP) |
| title | Evaluating the antagonist effect of naltrexone implant via opioid challenge tests with escalating doses of hydromorphone injection in former heroin dependent patients |
| title_full | Evaluating the antagonist effect of naltrexone implant via opioid challenge tests with escalating doses of hydromorphone injection in former heroin dependent patients |
| title_fullStr | Evaluating the antagonist effect of naltrexone implant via opioid challenge tests with escalating doses of hydromorphone injection in former heroin dependent patients |
| title_full_unstemmed | Evaluating the antagonist effect of naltrexone implant via opioid challenge tests with escalating doses of hydromorphone injection in former heroin dependent patients |
| title_short | Evaluating the antagonist effect of naltrexone implant via opioid challenge tests with escalating doses of hydromorphone injection in former heroin dependent patients |
| title_sort | evaluating the antagonist effect of naltrexone implant via opioid challenge tests with escalating doses of hydromorphone injection in former heroin dependent patients |
| topic | naltrexone opioid blockage opioid challenge hydromorphone long-acting naltrexone implant (NTX-IMP) |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1441598/full |
| work_keys_str_mv | AT weiqu evaluatingtheantagonisteffectofnaltrexoneimplantviaopioidchallengetestswithescalatingdosesofhydromorphoneinjectioninformerheroindependentpatients AT xuyiwang evaluatingtheantagonisteffectofnaltrexoneimplantviaopioidchallengetestswithescalatingdosesofhydromorphoneinjectioninformerheroindependentpatients AT chongyangdong evaluatingtheantagonisteffectofnaltrexoneimplantviaopioidchallengetestswithescalatingdosesofhydromorphoneinjectioninformerheroindependentpatients AT taozhang evaluatingtheantagonisteffectofnaltrexoneimplantviaopioidchallengetestswithescalatingdosesofhydromorphoneinjectioninformerheroindependentpatients AT shuguiyin evaluatingtheantagonisteffectofnaltrexoneimplantviaopioidchallengetestswithescalatingdosesofhydromorphoneinjectioninformerheroindependentpatients AT zhijunsun evaluatingtheantagonisteffectofnaltrexoneimplantviaopioidchallengetestswithescalatingdosesofhydromorphoneinjectioninformerheroindependentpatients AT shiqiangwang evaluatingtheantagonisteffectofnaltrexoneimplantviaopioidchallengetestswithescalatingdosesofhydromorphoneinjectioninformerheroindependentpatients AT anniguo evaluatingtheantagonisteffectofnaltrexoneimplantviaopioidchallengetestswithescalatingdosesofhydromorphoneinjectioninformerheroindependentpatients AT weihao evaluatingtheantagonisteffectofnaltrexoneimplantviaopioidchallengetestswithescalatingdosesofhydromorphoneinjectioninformerheroindependentpatients |