Urinary Diazepam Metabolite Distribution in a Chronic Pain Population

Diazepam is often used as an adjuvant to pain therapy. Cytochrome P450 (CYP) 3A4 and 2C19 metabolize diazepam into the active meta-bolites: nordiazepam, temazepam and oxazepam. Owing to diaze-pam’s side-effect profile, mortality risk and potential for drug–drug interactions with CYP 3A4 and/or CYP 2C19 inhibitors, urine drug testing (UDT) could be a helpful monitoring tool. This was a retro-spective data analysis that evaluated urine specimens from pain management practices for the distribution of diazepam metabolites with and without CYP 3A4 and 2C19 inhibitors. Intersubject nordiaze-pam, temazepam and oxazepam geometric mean fractions were 0.16, 0.34 and 0.47, respectively. Intrasubject geometric mean frac-tions were 0.157, 0.311 and 0.494, respectively. Sex, but not age or urinary pH, had an effect on metabolite fractions. Methadone signifi-cantly increased temazepam and oxazepam urinary fractions via CYP3A4 inhibition, whereas fluoxetine and esomeprazole increased nordiazepam fractions via CYP2C19 inhibition. Although more studies are needed, these results suggest the viability of UDT for increased monitoring for therapy and possible drug–drug interactions