Predicting metabolic side effects of transported drugs
View Patent ↗Provided are drug-transport metabolomics profile assessments and therapies.
1. A method for determining a drug therapy or efficacy, drug transporter-associated metabolic disease or disorder, or metabolic side effect in a subject, the method comprising
obtaining a biological sample from a subject, wherein the sample comprises a plurality of metabolites;
detecting an amount of each of the plurality of metabolites in the biological sample obtained from the subject,
identifying a single or plurality of drug transporter-associated metabolomics pathways by comparing each of the plurality of metabolites in the biological sample with drug-transport protein substrates associated with the single or plurality of drug transport-associated metabolomic pathways to obtain an drug-transport protein profile for the subject;
determining a pharmacophore profile for the subject for each drug-transport protein in the drug-transport protein profile;
determining a pharmacophore associated with one or a plurality of drugs to be administered to the subject; and
determining, based on the pharmacophore associated with the one or plurality of drugs and the pharmacophore profile for the subject, the effect a drug will have on metabolism in a subject.
2. The method of claim 1 , further comprising determining a difference between a control and subject's metabolites, wherein a difference is indicative of a drug transport-associated metabolic disease or disorder associated with a pharmacophore.
3. The method of claim 1 , further comprising identifying a drug therapy for the subject based upon the pharmacophore associated with the one or plurality of drugs and the pharmacophore profile of the subject.
4. The method of claim 1 , wherein the drug transport-associated metabolomics pathways are identified by analyzing a wild-type metabolic profile and a selected drug-transporter knockout metabolic profile and/or the metabolomics profile of a subject with altered expression and/or function of a drug transporter.
5. The method of claim 1 , wherein a metabolite or set of metabolites is monitored in a drug therapy for a modulation of a drug transporter metabolic profile to determine an efficacy of the drug and/or the presence of metabolic side effects.
6. The method of claim 1 , wherein the drug-transport protein profile comprises one or more SLC family of drug-transport proteins and/or one or more ABC family of drug-transport proteins.
7. The method of claim 6 , wherein the one or mom pharmacophore associated with the one or plurality of drugs are matched to the subject's drug-transport protein profile to identify a drug therapy.