I'm surprised the article didn't mention anything about pharmacogenetics. For example, drug-metabolizing enzyme polymorphisms can often lead to a 10+ fold difference in Cmax (or name the parameter) between a poor and an ultrarapid metabolizer of some enzyme.
Author here. Enzyme polymorphisms are tricky and would require a whole different blog post. Some drugs they matter a lot for, some drugs they do not. I actually have not found any drugs with 10-fold variability that could be ascribed solely (or even mainly) to polymorphisms, although it doesn't seem impossible.
Here’s an article I found in 30s of searching (granted, I already knew Warfarin was hugely affected by CYP2D6) stating that equivalent maintenance doses of Warfarin can vary by a factor of >10 (from 0.5mg to 7mg) based on the CYP2D6 phenotype of the patient.
Don't know about 10x, but having the MTHFR mutation genotype 667TT reduces folate activation [1] by 70-80%, which is a problem with drugs that require folate supplementation, like methotrexate.
Many tricyclic antidepressants metabolized by CYP2D6 would be here, if you put the nonmetabolizers up against the rapid metabolizer, https://en.wikipedia.org/wiki/Doxepin for example.
What about codeine with ultra-rapid metabolizers (e.g. the significant population in Saudi Arabia), it might not be a 10x difference but normal dosages can result in overdose or death in people that are ultra-rapid metabolizers or even in their babies if they are nursing mothers.
Warfarin is one of the most well known scientifically, but as a practitioner you may not know this because hospitals and insurers are scared to acknowledge the ongoing rate of preventable bad outcomes caused by not accounting for variances in metabolism.
That is to say, if we were to actually start assessing patients’ ability to metabolize warfarin we’d have to confront the fact that a huge number of bad clinical outcomes in the recent past stemmed from not doing this.
> hospitals and insurers are scared to acknowledge the ongoing rate of preventable bad outcomes caused by not accounting for variances in metabolism.
Healthcare systems are so aware of and open about warfarin's risks that they have warfarin clinics set up to repeatedly measure patients' prothrombin times so that they can adjust dosing empirically. Further, they also provide nutritional guidance to patients taking warfarin to help them reduce diet-influenced variance in warfarin metabolism.
