Verebey 1976: naltrexone's half-life and how long it blocks opioids

What they tested

Four people took naltrexone 100 mg by mouth, first as a single dose and later every day. Researchers measured naltrexone and its main breakdown product, beta-naltrexol, in blood, urine and stool. This kind of study is called pharmacokinetics: it tracks how a drug is absorbed, broken down and removed.

To see how well the drug blocked opioids, subjects were given 25 mg doses of heroin in the lab at set times after naltrexone, and their physical and self-reported responses were recorded.

What they found

After a single dose, naltrexone peaked in the blood at 1 hour, at an average of 43.6 ng/ml. Beta-naltrexol peaked at 2 hours, at 87.2 ng/ml. By 24 hours they had fallen to 2.1 and 17.6 ng/ml.

With daily dosing, peaks at 1 hour were 46.4 ng/ml for naltrexone and 158.4 ng/ml for beta-naltrexol, but by 24 hours both were back near single-dose levels. Steady state was reached quickly and neither built up in the blood. Half-lives changed little: 10.3 to 9.7 hours for naltrexone and 12.7 to 11.4 hours for beta-naltrexol.

Between 24 and 72 hours, naltrexone in the blood fell slowly from 2.4 to 1.7 ng/ml, a phase with an apparent half-life of 96 hours. In 24 hours, 38% of the dose left in urine after a single dose and 70% with daily dosing. Stool accounted for 2.1% and 3.6%.

Blockade of heroin was nearly complete through 48 hours. At 72 hours the physical responses to heroin came back more than the felt ones. Blood levels of naltrexone tracked closely with how well heroin was blocked (r = 0.91).

Limits

• Only 4 people took part, and the abstract doesn't describe who they were.
• Everyone took 100 mg, so the numbers may not match other doses or the monthly shot.
• The opioid blockade was tested with planned heroin doses in a lab, which says nothing directly about other opioids or real-world use.

What it means if you're considering naltrexone

For people asking how long naltrexone lasts, this small study gives some of the earliest numbers. Blood levels fell fast over the first day, didn't build up with daily doses, and low levels lingered for days. In the lab, the block on heroin lasted about 48 hours after a 100 mg dose.

It doesn't say how long a drug test would pick up naltrexone, or how to time it around opioid pain medicine. Those are questions for a prescriber.