Hi,
Does tenofovir enter every type of cell ? So besides the liver cell also the sperm cell, cells of the female egg, brain cell, heart cell, muscle cell etc ?
Br,
Hi @hepb1,
We of course know that it also enters immune cells (as it is used as an anti-HIV drug and HIV infects immune cells).
@john.tavis probably is the better person to answer this, but my understanding is that it does get into all cells, but likely at different rates: there have been studies labelling the drug and following it through the system of rats, showing this - https://journals.asm.org/doi/10.1128/aac.00419-09.
Thomas
Dear @hepb1 ,
The parental tenofovir (TFV) form (TFV diphosphate) is active against the reverse transciptase enzymes of both HIV and HBV and also stimulates the innate immune response by activation of the purine P1 receptor.
Unfortunately, TFV has impared transit across cell membrane and very poor mucosal transport, making its uptake into the blood very poor when taken orally.
Tenofovir disoproxil fumarate (TDF, aka viread etc) is a modifed form of TFV with greatly improved membrane and mucosal transport, making its uptake into the blood very efficient when taken orally.
TDF is taken up and converted to TFV in all cells of the body (except the CNS). This has no real toxic impact at clinically effective doses in any cells except those in the kidney (and mild kidney toxicity only occurs in a minority of patients after very long term exposure). This kidney toxicity can be reversed by lowering the TDF dosing frequency from daily to every other day or by switching to the more expensive version of TFV, TAF (tenofivir alafenamide).
Andrew has covered this very well!
John.
By analogy, we can think of the active form of tenofovir (TFV) as an inflatable lifeboat. A lifeboat only works when fully inflated, but in its active form it is unable to fit into our bodies and cells effectively. When this happens, our body just excretes the drug as it’s filtered out from the blood.
So what we do is modify the drug so that it is able to be transported around the body easily (like folding up the lifeboat and packaging it up) - this is what TDF and TAF are.
The cool trick is that once these drugs are inside the cell, the body’s enzymes essentially pull the cord of the lifeboats and inflate them. So they are no longer able to get OUT of the cell and so stay in the cell to do their job.
TAF is more tightly packed, so that it gets picked up by cells more easily. This means you can give less of it because more gets activated within the cells before being cleared away in the blood.
Hope this helps you visualise these concepts a bit easier.
Cheers,
TT
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