What is Tetrahydrofuran, and what is it doing in Plaxovid?

All credit goes to DrKatPhD here…..their twitter account was nuked for a week after they posted this information.  Discussion at the bottom of these photos.

OK.  A lot to unpack here.  Tetrahydrofuran is, per pubchem, not a safe chemical for any of us to be ingesting or breathing.  The solvent is used in the production of medications.  Of most recent note, it is being used in the production of Plaxovid.  We know Pfizer has been playing around with this polymer in pharma production for years, and faced a fine for contaminating waste water with it back in 2005.  17 years later, they are still playing with that chemical, this time with Plaxovid.

What I found interesting is the CYP450 pathways affected by Tetrahydrofuran.  CYP pathways are how the liver breaks down medications.  Different meds use different pathways.  Tetrahydrofuran affects the CYP1A2 and 2B10 pathways.  Different drugs and substances will either inhibit or slow the metabolism of other drugs in that pathway, or they will induce or speed up the metabolism of drugs in that pathway.

Lets look at CYP1A2 first.  The Pubchem article discusses the enhanced expression of mRNA in the pathway with tetrahydrofuran.  So I hypothesize, if we are ingesting or inhaling THF, will it mess with other medications that already USE that liver pathway for metabolism?  What other meds USE that 1A2 pathway?  Several it turns out!  Omeprazole, caffeine, Fluvoxamine, melatonin, ramelteon, tizanadine, cymbalta, cipro, clozapine, acyclovir.

What about the 2B10 pathway?  Here is the article I sourced.  https://www.frontiersin.org/articles/10.3389/fphar.2021.764124/full   This pathway works in conjunction with numerous OTHER pathways for overall drug excretion.  Part of the 2B10 pathway is regulation of our circadian rhythm, which is effected by period 2 or PER2 activation.  If the PER2 is stable, circadian rhythm is functioning.  If the PER2 is NOT stable, circadian rhythm is disrupted.  Studies also showed that when the PER2 was negative (not working) it impacted fatty liver, triglycerides, and cholesterol.  Inhibiting the 2B10 pathway “may exacerbate metabolic disorders and cause obesity by perturbing fatty acid metabolism, suggesting a role of CYP2B in lipid homeostasis (Heintz et al., 2019). These findings indicate a potential link between PER2 and CYP2B, particularly CYP2B10.”  CYP2B10/CYP2B6 activity is a critical determinant to the pharmacokinetics and efficacy of many drugs including CPA, ifosfamide, ketamine, pethidine, methadone, nevirapine and efavirenz.  In summary, CYP2B10 was down-regulated at the mRNA, protein, and enzymatic levels in Per2-deficient mice. Consistently, PER2 positively regulated CYP2B10 expression in both Hepa-1c1c7 and AML-12 cells. Moreover, PER2 regulated Cyp2b10 transcription in a REV-ERBα-dependent manner. Therefore, PER2 regulates CYP2B10 expression and activity through REV-ERBα, impacting the metabolism and pharmacokinetics of substrate drugs.

So my question becomes this:  The presence of Tetrahydrofuran at the 2B10 and 1A2 protein/enzyme substrates and the impact it has on the mRNA of those pathways……are we possibly using toxic substances to make pharma drugs that potentially alter your proteins and enzymes from functioning as they were designed to do?  Leading to more and more drug interactions?  Potentially turning off enzymes and proteins that prevent liver disease, obesity, lipid elevation?    One could hypothesize yes, because Plaxovid has a “drug interaction” list that is quite extensive.