Daily use of multiple medications is commonplace for many Americans. While pharmacists monitor prescriptions for drug interactions, consumers rarely check the possible side effects when using an over-the-counter product. In this fictional case study, Sam is prescribed clomipramine and ciprofloxacin, while also taking Tylenol PM.
All three medications are orally administered, and drug metabolism is catalyzed in the liver by cytochrome P450 enzymes (CYP450). CYP isoenzymes CYP1A2, CYP3A4 and CYP2C19 are responsible for clomipramine metabolism and formation of major bioactive metabolite desmethylclomipramine, while CYP2D6 hydroxylates clomipramine and metabolite into hydroxyclomipramine and hydroxydesmethylclomipramine, respectively. Multi-drug use can inhibit or induce metabolic activity.  The extent to which activity is affected is determined by dose and ligand-enzyme binding strength. Ciprofloxacin is a known CYP1A2 inhibitor, while diphenhydramine inhibits CYP2D6. Quantification and visualization of metabolites formed from clomipramine, ciprofloxacin, and diphenhydramine in rat liver microsomes was performed using compact mass spectrometry and high-performance liquid chromatography. Chromatograms were analyzed for molecular weights of parent clomipramine and metabolized products. Data indicated a reduction ranging from 21.1% to 30.1% inhibition of clomipramine metabolism into desmethylclomipramine. It was concluded that CYP isoenzymes CYP1A2, CYP3A4, and CYP2C19 played a role in diminishing clomipramine metabolite formation. These results illustrate the need for research and education when administering multiple drugs.

HPLC and CMS analysis of clomipramine metabolism: A multi-drug study

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