From the FDA Drug Label
Metabolism Diazepam is N-demethylated by CYP3A4 and 2C19 to the active metabolite N- desmethyldiazepam, and is hydroxylated by CYP3A4 to the active metabolite temazepam
The amount of temazepam produced from a given dose of diazepam is not explicitly quantified in the provided drug label. However, it is mentioned that diazepam is hydroxylated to temazepam by CYP3A4.
- The exact amount of temazepam produced cannot be determined from the given information.
- Temazepam is an active metabolite of diazepam, but the proportion of diazepam that is converted to temazepam is not specified 1.
From the Research
Diazepam does not directly convert to temazepam in a predictable dose-equivalent manner, and the amount of temazepam produced varies significantly between individuals, with approximately 10-15% of a diazepam dose eventually converted to temazepam through hepatic metabolism, as influenced by cytochrome P450 enzymes, particularly CYP3A4 and CYP2C19, which show genetic polymorphisms across populations 2. When considering the metabolism of diazepam to temazepam, it's crucial to understand that this process is complex and influenced by various factors, including genetics, liver function, age, and concurrent medications. The conversion of diazepam to temazepam occurs through N-demethylation of diazepam to nordazepam, followed by hydroxylation to temazepam.
- The most significant factor affecting this conversion is the activity of cytochrome P450 enzymes, specifically CYP3A4 and CYP2C19, which can vary significantly between individuals due to genetic polymorphisms 2.
- Additionally, factors such as liver function, age, and the presence of other medications that may inhibit or induce these enzymes can also impact the conversion rate of diazepam to temazepam.
- Given the variability in metabolism, clinicians cannot reliably predict the exact amount of temazepam that will result from a given dose of diazepam, making it essential to dose these medications independently when prescribed therapeutically.
- A study published in the Journal of Analytical Toxicology in 2014 found that the distribution of diazepam metabolites, including temazepam, can be affected by the presence of CYP3A4 and CYP2C19 inhibitors, further highlighting the complexity of diazepam metabolism 2.