Wondering how long hydrocodone stays in your system? On average, hydrocodone will stay in your system for about 11.4 hours. Note that this duration is just an estimate and does not apply to everyone. There are some caveats.
How Long Do The Effects of Hydrocodone Last?
Hydrocodone lingers in your body for around 12 hours, but the analgesic (pain-relieving) effects of hydrocodone are shorter.
According to one reference, pain relief begins after 30 minutes and last 4–8 hours[^1]. On the other hand, the package insert for hydrocodone states that the onset of action is 10–30 minutes and the drug's duration is 4–6 hours[^2]. The suggested dosing interval is 4–6 hours.
There are lots of reasons you might need to know how long Hydrocodone stays in your system. For example, you might wonder about how long hydrocodone lasts if:
- You need to pass a drug test
- You want to know when you’ll feel normal again (no longer under the influence of the drug)
- You take hydrocodone for pain management and want to estimate when you'll need to take another dose
- You're wondering when you'll stop feeling side effects of hydrocodone like nausea or constipation
- You need to take a different medication that is contraindicated by hydrocodone
Why Does It Take ~12 Hours For Hydrocodone To Be Excreted?
Earlier we said that Hydrocodone remains in your system for 11.4 hours. Here’s what that value is based on.
By definition, hydrocodone will be 87.5% eliminated from your body after 3 half-lives.
Since the half-life of hydrocodone is 3.8 hours, that means that after 11.4 hours (3 x 3.8 h) only 12.5% of the hydrocodone originally ingested will remain. So after 11.4 hours not all of the hydrocodone will be eliminated - just most of it (87.5%). That's why the 11.4 value is merely a convenient approximation.
Here’s a table to explain what I mean about half-lives:
|Half-life||Time||Hydrocodone Remaining (%)|
Factors That Affect The Clearance of Hydrocodone
Individual genetic differences affect how drugs are metabolized. The figure below shows hydrocodone levels over time. At t = 0 the study participants ingested hydrocodone. Next, a researcher measured the concentration in their bloodstream at regular intervals for up to 24 hours.
Consistent with what you'd expect, the study found that ultra-rapid metabolizers cleared the hydrocodone more quickly. The peak hydrocodone concentrations (Cmax) was also reduced in this group.
Poor and extensive metabolizers cleared the drug more slowly. Practically speaking, this means that if you’re an ultra-rapid metabolizer, hydrocodone might be cleared more quickly than 12 hours.
Hydrocodone Metabolism and CYP Enzymes
The individual differences in hydrocodone clearance are due to genetic variations in the cytochrome P450 enzymes that metabolize hydrocodone. These CYP enzymes are CYP2D6 and CYP3A4. Genetic variations affect the efficiency of the CYP enzymes that metabolize hydrocodone.
Metabolism of Hydrocodone Summary
- Hydrocodone is converted to hydromorphone by CYP2D6 which is the active analgesic.
- Hydrocodone is also metabolized by CYP3A4, but CYP3A4 forms norhydrocodone. Norhydrocodone is an inactive metabolite of hydrocodone.
- Pain relief correlates with hydromorphone levels, but not with hydrocodone levels.
- Current dosing strategies for opioids undergoing phase I metabolism do not account for pharmacogenetics, external 2D6 inhibitors/inducers or hydrocodone’s role as a pro-drug.
One study quantified hydrocodone and hydromorphone pharmacokinetics in CYP2D6 ultra-rapid metabolizer, extensive metabolizer, and poor metabolizer phenotypes (see above figure). A major aim of the study was to develop an hydrocodone phenotype-based dosing strategy for hydrocodone using clinical pharmacokinetics integrated with pharmacogenetics for patient safety.
Other Factors Affecting Hydrocodone Metabolism
So far we’ve discussed how genetics affect how long hydrocodone remains in your body after ingestion.
But there are other factors that can impact the clearance of hydrocodone. These include:
- Physiological differences like age, diet, and hormonal systems
- Diseases, especially conditions that impair liver or kidney function
- Genetic factors, like ethnic polymorphisms or individual differences
- Drug-drug interactions; drugs can inhibit or induce liver enzymes
Let's delve into these factors in greater detail.
- Age - the elderly clear hydrocodone more slowly. On the other end of the spectrum are infants which carry much lower capacity of oxidation (CYP450) and conjugation (UGT) compared to adults.
- Diet - Grapefruit juice contains compounds that inhibit CYP3A4, which metabolizes hydrocodone (see figure below). Grapefruit decreases the first pass effect and raises the bioavailability of many drugs like hydrocodone. Increasing drug bioavailability may increase risk and curative affect of adverse effects capacity of drug metabolism.
- Kidney function - Reduced kidney function tends to decrease the excretion of drug metabolites, Hydrocodone included.
- Liver function - Diseases that impair liver function affect Hydrocodone metabolism. Examples include hepatic cancer, cirrhosis and hepatitis, which can markedly increase the time Hydrocodone stays in your system.
- Prescription drugs - drugs that induce or inhibit CYP2D6 or CYP3A4 will affect how long hydrocodone stays in your system.
- CYP3A4 inhibitors will prolong the time Hydrocodone stays in your body and enhance the analgesic effects of the drug. Examples of CYP3A4 inhibitors include grapefruit and the antibiotic erythromycin.
- CYP3A4 inducers like modafinil or St. John's Wort hasten the clearance of Hydrocodone and reduce its analgesic effects. That's becuase CYP3A4 converts Hydrocodone to the inactive metabolite norhydrocodone.
- CYP2D6 inhibitors have a paradoxial effect on Hydrocodone. On the one hand, they will prolong the time that Hydrocodone stays in your system, yet they will reduce the analgesic effects of Hydrocodone. Examples of CYP2D6 inhibitors include SSRIs like Prozac or Zoloft.
- CYP2D6 inducers like dexamethasone will enhance the analgesic effect of Hydrocodone and its rate of elimination from the body.
- Genetics - Some patients claim they do not respond to codeine or codeine analogues as analgesic agents. It turns out that these patients (8% of Caucasians, 4% of African Americans and less than 1% of Asians) lack CYP2D6 which converts codeine to the active metabolite, morphine.
[^1]: Vallejo, R.; Barkin, R. L.; Wang, V. C. (2011). "Pharmacology of opioids in the treatment of chronic pain syndromes". Pain physician. 14 (4): E343–E360. PMID 21785485. [^2]: "Opioid (Narcotic Analgesics and Acetaminophen Systemic )". Retrieved 22 March 2014.