From the Guidelines
Benadryl (diphenhydramine) is primarily metabolized in the liver to its major metabolite, Nordiphenhydramine, as indicated in the study 1. The metabolism of Benadryl involves the conversion of diphenhydramine into less active metabolites through a process called first-pass metabolism.
- The major metabolite of Benadryl is Nordiphenhydramine, as shown in the study 1.
- This metabolism occurs mainly in the liver and involves various cytochrome P450 enzymes.
- The half-life of Benadryl is approximately 2-8 hours in adults, but can vary depending on factors such as age, liver function, and other medications being taken. Some key points to consider when evaluating the metabolism of Benadryl include:
- The liver's role in metabolizing the drug, with potential implications for patients with liver impairment.
- The involvement of cytochrome P450 enzymes, which can be affected by other medications that induce or inhibit these enzymes.
- The potential for drug interactions, such as with alcohol or other medications that compete for the same metabolic pathways. As noted in the study 1, the metabolism of Benadryl can be influenced by various factors, including age, liver function, and other medications being taken.
- For example, elderly patients or those with liver impairment may experience slower metabolism, leading to higher blood levels and increased side effects.
- Certain medications that inhibit CYP2D6, such as some antidepressants, may slow Benadryl's metabolism, while drugs that induce these enzymes may speed it up. Understanding the metabolism of Benadryl is crucial for safe and effective use, particularly in patients with liver disease or those taking other medications that may interact with Benadryl 1.
From the Research
Metabolism of Benadryl
- Benadryl, also known as diphenhydramine, is metabolized by the cytochrome P450 enzyme system in the liver 2.
- The specific P450 isozymes involved in the metabolism of diphenhydramine are CYP2D6, CYP1A2, CYP2C9, and CYP2C19 2.
- CYP2D6 is the primary enzyme responsible for the N-demethylation of diphenhydramine, with a high affinity for the substrate 2.
- Individuals who are ultrarapid metabolizers of CYP2D6 may be at higher risk for paradoxical excitation when taking diphenhydramine due to the rapid conversion of the drug to its active metabolites 3.
- Diphenhydramine can also inhibit the activity of CYP2D6, which can lead to increased levels of other drugs that are metabolized by this enzyme, such as hydrocodone 4.
Enzyme Inhibition
- Diphenhydramine has been shown to inhibit the activity of CYP2D6, which can lead to increased levels of other drugs that are metabolized by this enzyme 2, 4.
- The inhibition of CYP2D6 by diphenhydramine can lead to fatal drug interactions, as seen in the case of a woman who took diphenhydramine and hydrocodone/acetaminophen and experienced a fatal overdose 4.
- Other antihistamines, such as loratadine, have also been shown to inhibit the activity of CYP2D6 and other P450 enzymes 5.
Clinical Implications
- The metabolism of diphenhydramine can vary significantly between individuals due to differences in CYP2D6 activity 2, 3.
- Clinicians should be aware of the potential for drug interactions when prescribing diphenhydramine or other antihistamines to patients who are taking other medications that are metabolized by the P450 enzyme system 4, 5.
- Further studies are needed to fully understand the clinical implications of the metabolism of diphenhydramine and other antihistamines 3, 6.