Pharmacology and clinical experience with saquinavir.

Saquinavir is a peptidomimetic inhibitor of HIV protease. Initially marketed as Invirasetrade mark, the effectiveness of saquinavir was greatly hindered by its nearly complete first pass metabolism by cytochrome P450 3A4. A new formulation, Fortovasetrade mark, appears to yield some six times the drug exposure and has been demonstrated to yield virological and immunological results similar to those of other protease inhibitors (PIs) when used in conjunction with two nucleoside reverse transcriptase inhibitors (nRTIs). Emerging data suggest it is safe to use twice daily. Co-administration of either formulation of saquinavir with nelfinavir and especially ritonavir yields greatly increased blood levels, with corresponding superior magnitude and durability of viral suppression in first line therapy, albeit with increased adverse effects. The combination of ritonavir and saquinavir has also yielded the most promising results published for second line therapy, after virological breakthrough on previous PI-containing therapy. In addition, preliminary data suggests the possibility of once daily dosing of ritonavir and saquinavir, which would be expected to increase compliance and allow for direct observed therapy.