In some cases, we add rotinavir to invirase to enhance the bioavailability of invirase.
Generally, presystemic metabolism of drugs leads to low bioavailability particularly when the drug is effluxed by P-glycoprotein membrane protein which is co-localized with CYP3A4 enzyme.
Saquinavir is a drug which is metabolized by CYP3A4 enzyme. Saquinavir is a protease inhibitor. Invirase contains saquinavir in solid dosage forms like tablets or hard gelatin capsule while Saquinavir, in Fortovase, formulated as self emulsifying drug delivery system available in soft gelatin capsule. This formula of Fortovase leads to a better bioavailability than Invirase. This can be attributed to the greater dissolution enhancement of drug due to the greater reduction of particle size after emulsification in the GIT. The rapid dissolution leads to escape of the drug from the metabolizing enzymes.
The difference in the bioavailability between the the two drug products leads to addition of rotinavir as inhibitor of CYP3A4 to make Invirase bioavailability similar approximately to Fortovase. However, FDA decided to discontinue the use of Fortovase due to the lower need of drug. This decision is not related to any efficacy or side effects but due to patient aesthetics which comes from the need of keeping of Fortovase in refrigirator.
As far as I know, the standard approach is to add ritonavir (or cobicistat) whenever a protease inhibitor (like saquinavir) is administered. In other words, boosted HIV PI therapy is the standard and unboosted HIV PI-based regimens have become an exception.
Whereas a formulation that promotes the dissolution of saquinavir may enhance the bioavailability (also) by saturating intestinal CYP enzymes, ritonavir will certainly also affect hepatic CYP3A activity, thus influence the half-life of saquinavir. The latter may not be achieved through the formulation.
I am not sure what is meant by "patient aesthetics", but it is clear that a formulation that can be stored at room temperature is preferred over a formulation that expires within 3 months, except when kept in the fridge.
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