Drugs and supplements are metabolized in the body using various chemical changes.
These changes allow the drugs to be excreted through urine and faeces.
Metabolism can occur through the kidneys; by transformation into metabolites, the skin, the intestines, and the most commonly used method, the P450 enzyme system in the liver.
The P450 system involves many liver enzymes, however, the most used enzyme is CYP3A4. This enzyme is particularly important for processing steroids, for bile duct excretion and for clearing excess hormones and phytochemicals (plant chemical compounds) found in food. The latter makes it particularly important for clearing excess hormones in the body.
Other common enzymes are CYP1A2, CYP2D6, CYP2E1, CYP2C9 and CYP2C19. These can sometimes be a primary enzyme for metabolism with CYP3A4 as a secondary.
The focus here is on CYP3A4 as this is the main enzyme used.
Drugs using these liver enzymes for metabolism are often referred to as a SUBSTRATE.
A number of drugs and supplements can interact with the liver enzymes in one of two ways.
INHIBITORS of enzymes will slow down clearance of the SUBSTRATE (main drug or treatment) in the liver to make it more toxic and potentially elevate liver enzymes. This can put more stress on the liver.
INDUCERS of enzymes will push the SUBSTRATE through the liver too quickly and will potentially make the drug weaker and less effective.
There are far more inhibitors than inducers.
Common inhibitors of CYP3A4
Amiodarone
Amprenavir
Aprepitant
Atazanavir
Bitter Orange (Juice form; not supplements)
Cat’s Claw
Chloramphenicol
Cimetidine
Clarithromycin
Conivaptan
Curcumin
Cyclosporine
Darunavir
Dasatinib
Delavirdine
Diltiazem
EGCG (Green Tea)
Erythromycin
Fluconazole
Fluoxetine
Fluvoxamine
Fosamprenavir
Grapefruit
Grapeseed Extract
Imatinib
Indinavir
Itraconazole
Ketoconazole
Lapatinib
Miconazole
Nefazodone
Nelfinavir
Piperine greater than 10mg (often found in curcumin products)
Posaconazole
Ritonavir
Quinupristin
Saquinavir
Tamoxifen
Telithromyci
Verapamil
Voriconazole
Common inducers of CYP3A4
Aminoglutethimide
Bexarotene
Bosentan
Carbamazepine
Dexamethasone
Echinacea
Efavirenz
Fosphenytoin
Ginkgo
Griseofulvin
Liquorice
Modafinil
Nafcillin
Nevirapine
Oxcarbazepine
Phenobarbital
Phenytoin
Primidone
Rifabutin
Rifapentine
Rooibos
St John’s Wort
All drugs have an elimination half-life. This is the time it takes to reach 50% concentration in the body.
If you know the half-life (which can easily be found by using Google), you can calculate when it is safe to reintroduce any supplement or medication that may interact with treatment.
Some drugs are metabolized in the body using the kidneys; however, many are metabolized through the P450 system of liver enzyme.
Example:
100mg of a drug has a half-life of 60 minutes.
60 minutes after taking it the levels are down to 50mg
120 minutes = 25mg
180 minutes = 12.5mg
240 minutes = 6.25mg
360 minutes = 3.125mg
In theory, the dose will down by 97% after 5 x the half-life.
It is considered to have a negligible effect at this level.
