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- Please note
- The information presented here is NOT A COMPLETE LIST of OCT2 inducers, inhibitors, and substrates
- Not all drug interactions are clinically significant. Potential drug interactions should be researched, and medication changes should only be made after consulting a health professional.
- ACRONYMS AND DEFINITIONS
- CYP - Cytochrome P450
- OCT - Organic Cation Transporter
- Substrate - a drug that is metabolized by a certain enzyme is a substrate of that enzyme
- ORGANIC CATION TRANSPORTER 2 (OCT2) OVERVIEW
- Overview
- OCT2 is sometimes referred to by its gene name, "SLC22A2"
- OCT2 is a transport protein found in the kidney. It is located in the membrane of tubular epithelial cells in the proximal convoluted tubule.
- OCT2 transports drugs that have a positive charge (cations) from the blood supplying the proximal tubule to the inside of the tubular epithelial cell
- Another transport molecule, "Multidrug and toxin extrusion proteins (MATE)," transports the cationic drug from inside the cell into the tubular lumen for excretion in the urine
- OCTs are located in the following tissues
- OCT1 - liver
- OCT2 - kidney and brain
- OCT3 - skeletal muscle, liver, placenta, kidney, heart
- OCT2 drug interactions
- Inducers and Inhibitors
- Inducers - increase the activity of OCT2 (no OCT2 inducers have been discovered)
- Inhibitors - block the action of OCT2
- When OCT2 inhibitors are taken with medications that are transported by OCT2, they can alter the elimination of that medication
- Drugs may be transported by OCT2 and also inhibit it at the same time
- Competitive inhibition
- If two drugs are transported by OCT2, they may "compete" for it, and this can alter the elimination of one or both of the drugs
- Compounded interactions
- When a person is taking three or more drugs, the potential for compounded interactions exists
- Example:
- Drug A is metabolized by CYP2D6, and it is transported by OCT2
- Drug B inhibits CYP2D6. Drug C inhibits OCT2.
- When Drug A is taken with Drug B, its elimination is partially decreased, but it is not significant
- When Drug A is taken with Drug B and Drug C, its elimination is decreased substantially and the interaction becomes significant
- Genetic factors
- OCT2 is coded for by a gene called SLC22A2
- Since individuals vary in their genetic makeup, their SLC22A2 gene may also vary
- Some people have SLC22A2 genes that produce OCT2 molecules that are less effective
- Genetic variations in the SLC22A2 gene can affect how an individual eliminates a drug
- IMPORTANT POINTS ABOUT DRUG INTERACTIONS
- Drug interactions are challenging
- Information on drug interactions can be difficult to assimilate
- Certain drug interactions and metabolic pathways are well-documented while many are not
- Factors that can make drug interactions challenging
- New drugs
- When a new drug is being developed, the FDA requires that it be tested for drug interactions with a small number of medications that are known to have significant interactions
- Obviously, there is no way to test a medication in every possible drug combination that may occur. This means most drugs come to market with incomplete drug interaction profiles.
- After a medication is prescribed to a large number of people, other drug interactions are inevitably discovered
- Research
- Much of the research involving drug metabolism and drug interactions occurs in vitro meaning in a lab, or outside of the human body
- Animal models and cell cultures are often used to test drugs for metabolic pathways and interactions
- Findings from in vitro experiments do not always translate into what actually happens in the human body (in vivo)
- Evolving information
- Drug metabolism is an evolving field of medicine and pharmacology
- Researchers are just beginning to understand all the different systems that are involved in how the body metabolizes and eliminates drugs
- Cell transport systems (ex. p-glycoprotein, OAT, etc.) are a relatively new area of pharmacology and information about how these systems affect drug elimination is evolving
- Important points
- Not all drug interactions are known or can be predicted
- Good information on possible drug interactions may not be available
- Not all drug interactions are significant
- Always consult your physician or pharmacist before changing your medication if you are concerned about a possible drug interaction
- OCT2 AND CREATININE
- Creatinine is a byproduct of muscle metabolism (see creatinine for more)
- Serum creatinine levels are widely used as an indirect measure of kidney function
- Creatinine is filtered at the kidney glomerulus (see GFR), and it is also secreted into the urine by OCT2 (OCT2 substrate)
- OCT2 inhibitors may cause a rise in serum creatinine levels which may be falsely interpreted as a decrease in kidney function [2]
- OCT2 INDUCERS
- No OCT2 Inducers have been discovered
- OCT2 INHIBITORS
- OCT2 inhibitors
- Adapalene (Differin®) [1]
- Benztropine (Cogentin®) [1]
- Bupropion (Wellbutrin®, Contrave®) - [3]
- Cimetidine (Tagamet®) - is a more potent MATE inhibitor [1,4]
- Chlorhexidine [1]
- Desipramine (Norpramin®) [4]
- Dicyclomine (Bentyl®) [1]
- Dipyridamole (Persantine®) [1]
- Disopyramide (Norpace®) [1]
- Dolutegravir (Tivicay®) [3]
- Epinastine (Elestat®) [1]
- Exemestane (Aromasin®) [1]
- Guanabenz [1]
- Imatinib (Gleevec®) [1]
- Imipramine (Tofranil®) [1]
- Ipratropium (Atrovent®, etc.) [1]
- Lamotrigine (Lamictal®) [3]
- Olanzapine (Zyprexa®) [1]
- Ondansetron (Zofran®) [1]
- Orphenadrine (Norflex®) [1]
- Pentamidine (Pentam®) [1]
- Phenoxybenzamine (Dibenzyline®) [4]
- Propantheline bromide [1]
- Quinidine [4]
- Quinine (Qualaquin®) [4]
- Rabeprazole (Aciphex®) [1]
- Ranolazine (Ranexa®) [6]
- Sulconazole (Exelderm®) [1]
- Tolterodine (Detrol®) [1]
- Trimethoprim (Bactrim®) [3]
- Vandetanib (Caprelsa®) [3]
- OCT2 SUBSTRATES (DRUGS TRANSPORTED BY OCT2)
- OCT2 substrates
- Amantadine [4]
- Amiloride (Midamor®) [4]
- Cimetidine (Tagamet®) [4]
- Creatinine - see creatinine above
- Dofetilide (Tikosyn®) [4]
- Dopamine [4]
- Famotidine (Pepcid®) [4]
- Memantine (Namenda®) [4]
- Metformin (Glucophage®) [4]
- Oxaliplatin (Eloxatin®) [4]
- Pindolol (Visken®) [4]
- Procainamide [4]
- Ranitidine (Zantac®) [4]
- Trimethoprim (Bactrim®) [3]
- Varenicline (Chantix®) [4]
- BIBLIOGRAPHY
- 1 - PMID 21599003 - OCT2 profile study
- 2 - PMID 23435786 - OCT2 review
- 3 - Manufacturer's Package Insert
- 4 - FDA drug development and drug interactions - CLICK HERE
- 5 - PMID 22072731
- 6 - Glucophage PI