Polypharmacy, involving co-administration of several drugs, is common among the elderly and chronically ill.  It is a risk factor for adverse drug reactions (ADRs) and drug-drug interactions (DDIs). One plausible DDI occurs when a drug interferes with another, causing irreversible changes to formation of metabolites from one or both. Such suppression or attenuation of metabolism could cause variances in toxicity and efficacy. We report experiments to predict and confirm modulation of oxidative metabolites from several combinations of common drugs for cancer, diabetes, hypercholesterolemia and hypertension in the presence of each other. Recent papers indicate best evidence for the dimerization of some compounds in dilute aqueous solution or assorted complex formation between disparate compounds. Biomimiks� technology (in vitro and ex vivo) is designed to mimic the in vivo oxidative metabolism mediated by cytochromes P450. This can be applied at the individual patient level for chemistry-based diagnostics to determine comparative effectiveness and safety.

Chemosynthetic livers: Evaluating plausible drug-drug interactions relating to metabolite suppression or attenuation with Biomimiks�

248th National Meeting (2014)

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