Thanks for the post on drug intercations. I think you hit the nail with the example of CYP3A4 induction by St. Johns wort. Rifampin, known as prototypical CYP3A4 inducer has been contraindicated for coadministration with several drugs like statins, some of the protease inhibitors etc. Often one can notice in the drug label that grape fruit juice should be avoided during the intake of a specific medication. This is because of its CYP3A4 inhibition potential, thereby increasing the plasma concentrations of co administered drug and causing un wanted adverse events. Drug interactions gets even complicated when the same drub is an inducer or inhibitor of transporters lik PgP or OATP. With new transporters emerging every now and then, I wonder how one would go about evaluating drug interactions. Any thoughts?

Janelle, there are guidelines from the FDA about how to test for possible drug interactions. Rather than test against individual drugs, we use the mechanism behind the potential interaction to make the comparison. I’ll give an example:

CYP3A4 (mentioned in the post above) and another enzyme CYP2D6 are two of the P450 enzymes in the liver. Together they are responsible for the metabolism of about 75% of all drugs. This means that any drug that affects the function of these enzymes (as SJW did with 3A4) will have a high chance of changing the effects of another drug.

When a drug is prepared for clinical trials the metabolic profile is determined and the extent to which every (or at least the high abundance) enzyme contributes to the metabolism is known.

Then, when prescriptions are written and delivered the metabolic profiles of the drugs are compared by computer (and some common ones should be known by doctors and pharmacists) to look for potential drug interactions.

Herbal and “natural” supplements can get you into trouble as well because of interaction with other drugs and/or the components they themselves contain. There was a report a few years ago of an owner giving his dog chinese medicine balls instead of more traditional western medicine because he thought it was a more natural therapy (I cannot remember the ailment at the moment). The dog subsequently died. A necropsy and analysis of the medicine balls revealed toxic levels of mercury and lead, not to mention numerous herbs that were mixed in. The natural chinese balls were entirely natural, but deadly. Natural does not always equal good and safe.

You’re welcome to make use of the post as long as you link back here with the appropriate credit.

Drug metabolism is a much deeper field than I’ve outlined above and smoking is certainly a complicating factor. If you want to learn more look up information about the cytochrome P450 monooxygenases and xenobiotic metabolism as a place to start. A textbook like Goodman and Gilman’s “The Pharmacological Basis of Therapeutics” is another excellent and extensive source of information.

I have often used the word ‘metabolism’ in my website and article warnings about the risks of combining even vitamins and herbal products such as St. John’s Wort with hormonal contraceptives, yet I worry that this information is easily ’scrolled past’ or dismissed in the urgency to prevent pregnancy.

Your explanation, however, will ‘back up’ these warnings and hopefully encourage women, particularly those who are just starting their ‘contraception career’ to learn all they can about the ‘drugs’ they are putting into their bodies.

Understanding a bit more about individual metabolism and how their body reacts when they artificially alter their hormone levels will also help them to understand and successfully manage the ‘trial and error’ period when selecting a hormonal type of birth control.

Thank you