From the FDA Drug Label
Ivermectin is metabolized in the liver, and ivermectin and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1% of the administered dose excreted in the urine. In vitro studies using human liver microsomes and recombinant CYP450 enzymes have shown that ivermectin is primarily metabolized by CYP3A4 Depending on the in vitro method used, CYP2D6 and CYP2E1 were also shown to be involved in the metabolism of ivermectin but to a significantly lower extent compared to CYP3A4
Ivermectin is metabolized in the liver by the enzyme CYP3A4, with CYP2D6 and CYP2E1 also involved to a lesser extent 1. The metabolites are then excreted primarily in the feces.
From the Research
Ivermectin is primarily metabolized in the liver through the cytochrome P450 enzyme system, specifically the CYP3A4 isoenzyme, as confirmed by the most recent study in 2024 2. This metabolism process involves the conversion of ivermectin into at least ten metabolites, with the two major ones being 3"-O-demethyl ivermectin and 4a-hydroxy ivermectin. The key points to consider in ivermectin metabolism include:
- Extensive hepatic first-pass metabolism, where most of the drug is transformed before entering systemic circulation 3
- Primary excretion of metabolites in feces, with less than 1% of the administered dose being eliminated in urine 4
- A half-life of approximately 18 hours in humans, though this can vary based on individual factors such as age, liver function, and concurrent medications 5
- Potential for drug interactions due to ivermectin's reliance on CYP3A4 for its metabolism, which can be affected by inhibitors or inducers of this enzyme 2, 4 It is essential to consider these factors when evaluating potential drug interactions and optimizing ivermectin therapy. Some of the key metabolites of ivermectin include:
- 3"-O-demethyl ivermectin (M1)
- 4-hydroxymethyl ivermectin (M3)
- 3"-O-demethyl, 4-hydroxymethyl ivermectin (M6) These metabolites are produced primarily by CYP3A4, with a small contribution from CYP3A5 5. Overall, understanding the metabolism of ivermectin is crucial for optimizing its therapeutic use and minimizing potential adverse effects.