Urinary metabolic ratio of pain management and substance abuse treatment drugs: Drug–drug interactions

Abstract

We present data showing that the urinary metabolic ratio (MR) of metabolite to parent drug can be used to estimate the drug–drug interactions (DDIs) of pain management and substance abuse treatment medications with other coadministered drugs. We quantitatively measure 18 drugs and their phase I metabolites and monitor the effects of 14 interfering drugs on their MRs. The 18 drugs include dextromethorphan, oxycodone, hydrocodone, tramadol, morphine, buprenorphine, fentanyl, clonazepam, alprazolam, quetiapine, carisoprodol, tapentadol, ketamine, methadone, impramine, and amitriptyline. The 14 interfering drugs include fluoxetine, paroxetine, bupropion, citalopram, sertraline, venlafaxine, duloxetine, risperidone, trazodone, aripiprazole, cyclobenzaprine, amphetamine, and tetrahydrocannabinol. Some of these interfering drugs are inhibitors of either the CYP2D6, CYP3A4/5, or CYP2C19 pathways. By using the urinary MR of metabolite/parent drug, we observed patterns of inhibition and enhancement due to DDIs. Using the MR reference intervals of the 18 drug pairs established in an earlier study, and the current DDI system, we can alert providers of unusual metabolism caused by DDIs. This will help providers do better prescribing or review more closely all medications and supplements patients are taking, thus avoiding underdosing or potential medication adverse reactions.