Question
How does ritonavir (Norvir) work?
8 July 2010. Related: All topics, Drug interactions.
Can you explain how ritonavir (Norvir) works with other protease inhibitors (PIs) to make them more effective. Why not just use a larger does of the PI? If ritonavir is to make PIs assimilate better into the blood stream, would pancreatic supplements work just as effectively?
Bob
Answer
Hi Bob,
Thank you for your question. It is a very good question to ask.
The liver is the organ in the body where any drugs you take are filtered from your blood. It is also the organ where some tablets undergo a series of chemical changes to make them into something the body can digest and use. This process of chemical changes is referred to ‘metabolism’. The proteins which cause this change are called enzymes.
Protease inhibitors are metabolized by a particular enzyme in the liver called cytochrome P450-P3A4 (CYP3A4). Ritonavir interacts with the CYP3A4 which slows down the metabolism of the PI. This means there is a more even amount of PI in the blood stream which is important to avoid side effects (from levels that are too high) and prevent resistance (from levels that are too low). This is best shown using a graph which can be seen by following this link.
By adding more PI and no ritonavir the levels of PI will start off very high and then get very low too quickly. The alternative would be to take PI tablets much more frequently each day to keep the levels of drug in the blood stream adequate. This is not a good solution as the more tablets that need to be taken the more likely we are to get problems with adherence.
Using a boosted PI appears to be the best way of ensuring an effective dose is maintained with the least amount of side effects meaning the drugs are more tolerable.
Pancreatic supplements do not slow down the CYP3A4 pathway and so would not reduce the speed that PIs are metabolized by the liver enzymes.
For further information please follow this link
If you are on ritonavir don’t forget that it can also boost the effect of other commonly used drugs. I recently started taking Viagra that I bought over the internet and found that it worked very quickly and over a prolonged period of time. On checking with my HIV doctor he advised me that I should only use a half (or less) of the usual prescribed dose as ritonavir has been found to strongly boost the effect of Viagra and similar drugs.