Drug Evaluation: Anti-infectives: Saquinavir: A review of its development, pharmacological properties and clinical use

Abstract

Saquinavir is an inhibitor of the HIV proteinase enzyme which has demonstrated potent in vitro activity and acceptable pharmacokinetics. In completed Phase I/II clinical studies, saquinavir has demonstrated antiviral activity both as a monotherapy at doses up to 7200 mg/day and in combination with zidovudine and zidovudine/zalcitabine at 1800 mg/day. Activity has been demonstrated in patients both experienced with and naive to antiretroviral therapy and CD4 cell counts up to 500/mm3. Resistance to saquinavir has been reported both in vitro and from clinical isolates and characteristic mutations have been described. Saquinavir does not appear to select for virus cross-resistant to either indinavir or ritonavir, the other proteinase inhibitors in advanced development. Additionally, saquinavir resistance appears relatively slow to develop, may be further delayed in combination use and, importantly, may delay zidovudine resistance. Saquinavir has an excellent safety profile with few adverse events reported to date. Saquinavir represents an active antiretroviral agent, with potential for use as a combination agent across the spectrum of HIV disease.

Key Words:

• saquinavir
• HIV proteinase
• antiretroviral activity
• HIV infection