TY - JOUR
T1 - Opioid challenge evaluation of blockade by extended-release naltrexone in opioid-abusing adults
T2 - Dose-effects and time-course
AU - Bigelow, George E.
AU - Preston, Kenzie L.
AU - Schmittner, John
AU - Dong, Qunming
AU - Gastfriend, David R.
N1 - Funding Information:
Funding for the study was provided by Alkermes, Inc., Cambridge, MA (manufacturer of XR-NTX) and by the Intramural Research Program , National Institute on Drug Abuse , National Institutes of Health . The Hopkins site was funded by Alkermes ; the Intramural Research Program site of the National Institute on Drug Abuse was self-funded . Alkermes provided funding for the preparation of the manuscript and participated in the analysis of the data, the writing of the manuscript, and the decision to submit the paper for publication. The Medisorb ® preparation used in XR-NTX was developed with support from National Institute on Drug Abuse Grant R43DA013531 and National Institute on Alcohol Abuse and Alcoholism Grant N43AA001002 .
PY - 2012/6/1
Y1 - 2012/6/1
N2 - Background: Oral naltrexone's effectiveness as an opioid antagonist has been limited due to poor patient adherence. A long-acting naltrexone formulation may be beneficial. This study evaluated the effects of extended-release injectable naltrexone (XR-NTX), targeted for a one-month duration of action, in blocking opioid agonist challenge effects in humans. Methods: Outpatient non-dependent opioid abusers (N= 27) were randomly assigned to a single double-blind IM administration of 75, 150, or 300. mg XR-NTX. To assess the extent of opioid blockade, hydromorphone challenges (0, 3, 4.5, 6. mg IM in ascending order at 1-h intervals [up to 13.5. mg total]) were given at pretreatment baseline and on days 7, 14, 21, 28, 42, and 56. Opioid blockade was assessed via (1) tolerability of the ascending hydromorphone doses; (2) visual analog scale (VAS) ratings of subjective opioid effects and (3) pupil diameter. Effects on the VAS and pupils were assessed via the slope of the time-action function over ascending hydromorphone doses, with zero slope indicating complete blockade. Results: Blockade of the VAS " any drug effect" response to 3. mg hydromorphone was complete for 14, 21, and 28 days, respectively, for the XR-NTX doses of 75, 150, and 300. mg. Subjective effects were more readily blocked than was pupil constriction. Higher hydromorphone doses produced only modest increases in agonist effects. With the 300. mg XR-NTX dose the slope of VAS responses remained at or near zero for one month even with maximal cumulative hydromorphone dosing. Conclusions: These data quantify the month-long opioid blockade underlying XR-NTX's efficacy in opioid dependence treatment.
AB - Background: Oral naltrexone's effectiveness as an opioid antagonist has been limited due to poor patient adherence. A long-acting naltrexone formulation may be beneficial. This study evaluated the effects of extended-release injectable naltrexone (XR-NTX), targeted for a one-month duration of action, in blocking opioid agonist challenge effects in humans. Methods: Outpatient non-dependent opioid abusers (N= 27) were randomly assigned to a single double-blind IM administration of 75, 150, or 300. mg XR-NTX. To assess the extent of opioid blockade, hydromorphone challenges (0, 3, 4.5, 6. mg IM in ascending order at 1-h intervals [up to 13.5. mg total]) were given at pretreatment baseline and on days 7, 14, 21, 28, 42, and 56. Opioid blockade was assessed via (1) tolerability of the ascending hydromorphone doses; (2) visual analog scale (VAS) ratings of subjective opioid effects and (3) pupil diameter. Effects on the VAS and pupils were assessed via the slope of the time-action function over ascending hydromorphone doses, with zero slope indicating complete blockade. Results: Blockade of the VAS " any drug effect" response to 3. mg hydromorphone was complete for 14, 21, and 28 days, respectively, for the XR-NTX doses of 75, 150, and 300. mg. Subjective effects were more readily blocked than was pupil constriction. Higher hydromorphone doses produced only modest increases in agonist effects. With the 300. mg XR-NTX dose the slope of VAS responses remained at or near zero for one month even with maximal cumulative hydromorphone dosing. Conclusions: These data quantify the month-long opioid blockade underlying XR-NTX's efficacy in opioid dependence treatment.
KW - Depot naltrexone
KW - Extended-release naltrexone
KW - Hydromorphone
KW - Injectable naltrexone
KW - Naltrexone
KW - Opioid blockade
KW - Opioid challenge
KW - Vivitrol
UR - https://www.scopus.com/pages/publications/84861225663
UR - https://www.scopus.com/pages/publications/84861225663#tab=citedBy
U2 - 10.1016/j.drugalcdep.2011.10.018
DO - 10.1016/j.drugalcdep.2011.10.018
M3 - Article
C2 - 22079773
AN - SCOPUS:84861225663
SN - 0376-8716
VL - 123
SP - 57
EP - 65
JO - Drug and alcohol dependence
JF - Drug and alcohol dependence
IS - 1-3
ER -