Subsequent trials in Norway and the US did compare injectable naltrexone to buprenorphine and found them to be similar in outcomes for patients willing to undergo the withdrawal symptoms required prior to naltrexone administration. Nearly 30% of patients in the US trial did not complete induction. In real world settings, a review of more than 40,000 patient records found that while methadone and buprenorphine reduced risk of fatal overdose, naltrexone administration showed no greater effect on overdose or subsequent emergency care than counseling alone.Despite these findings, naltrexones manufacturer and some health authorities have promoted the medicine as superior to methadone and buprenorphine since it is not an opioid and does not induce dependence. The manufacturer has also marketed directly to law enforcement and criminal justice officials, spending millions of dollars on lobbying and providing thousands of free doses to jails and prisons. The technique has been successful, with the criminal justice system in 43 states now incorporating long-acting naltrexone. Many do this through Vivitrol courts that offer only this option, leading some to characterize this as "an offer that cannot be refused." The companys marketing techiques have led to a Congressional investigation, and warning from the FDA about failure to adequately state risks of fatal overdose to patients receiving the medicine.In May 2017, United States Secretary of Health and Human Services Tom Price praised [Vivitrol] as the future of opioid addiction treatment after visiting the companys plant in Ohio.
It is also thought to be involved in the effectiveness of naltrexone in alcohol dependence by reducing the euphoric effects of alcohol. The role of KOR modulation by naltrexone in its effectiveness for alcohol dependence is unclear but this action may also be involved based on theory and animal studies. Other activities
In addition to the opioid receptors, naltrexone binds to and acts as an antagonist of the opioid growth factor receptor (OGFR) and toll-like receptor 4 (TLR4) and interacts with high- and low-affinity binding sites in filamin-A (FLNA). It is said that very low doses of naltrexone (<0.001–1 mg/day) interact with FLNA, low doses (1 to 5 mg/day) produce TLR4 antagonism, and standard clinical doses (50 to 100 mg/day) exert opioid receptor and OGFR antagonism. The interactions of naltrexone with FLNA and TLR4 are claimed to be involved in the therapeutic effects of low-dose naltrexone. Pharmacokinetics
The absorption of naltrexone with oral administration is rapid and nearly complete (96%). The bioavailability of naltrexone with oral administration is 5 to 60% due to extensive first-pass metabolism. Peak concentrations of naltrexone are 19 to 44 μg/L after a single 100 mg oral dose and time to peak concentrations of naltrexone and 6β-naltrexol (metabolite) is within 1 hour.