Saquinavir-soft gel: establishing saquinavir in HAART regimens

Abstract

The initial formulation of the HIV protease inhibitor (PI) saquinavir (SQV) in hard gel capsules (Invirase®) demonstrated significant clinical benefit in double and triple combination regimens in comparative studies. However, pharmacological limitations of this preparation resulted in fewer patients achieving optimal treatment responses than observed with other PIs. Changes in formulation and dosing to a new soft gelatin capsule formulation of SQV (SQV-SGC, Fortovase®) result in an average 8-fold increase in SQV exposure with SQV-SGC. Data from clinical trials indicate that this enhanced plasma exposure translates into more potent antiviral activity, with small comparative studies suggesting activity to be similar to other available PIs in triple therapy highly-active antiretroviral therapy (HAART) regimens. Additionally, SQV-SGC appears to be an excellent candidate for PI combination use. SQV-SGC appears well-tolerated with a low incidence of mainly gastrointestinal side-effects. The lower affinity to P450 isozymes of SQV means that the incidence of drug interactions is low, indeed probably lower than with other approved members of this class. Current obstacles to SQV-SGC’s widespread use include only limited, short-term bid dosing data (outside of combination with ritonavir) and the pill burden of 18 capsules per day.