Fosamprenavir Calcium

Fosamprenavir is a prodrug of amprenavir, a potent inhibitor of the HIV-1 protease. The drug is rapidly hydrolyzed to amprenavir in vivo, and the active metabolite binds to the active site of HIV-1 protease, preventing the cleavage of viral Gag and Gag-Pol polyprotein precursors. This inhibition results in the formation of immature, non-infectious viral particles. Fosamprenavir is extensively metabolized by CYP3A4, and its pharmacokinetics are significantly affected by coadministration with ritonavir, a potent CYP3A4 inhibitor that boosts amprenavir exposure. In a pharmacokinetic study involving healthy subjects, fosamprenavir was administered at 700 mg twice daily with ritonavir 100 mg twice daily for 10 days. The study evaluated the effect of rifabutin on fosamprenavir pharmacokinetics and demonstrated that coadministration significantly altered the plasma concentration-time profiles of both fosamprenavir and its active metabolite amprenavir.

Fig. 1 Summary of mean white blood cell (WBC) and neutrophil counts over time. (Ford S L.; et al. 2008)

A therapeutic deep eutectic solvent formulation of fosamprenavir calcium was developed by dissolving the drug in a 1:2 molar ratio mixture of choline chloride and urea. COSMO-RS screening identified five candidate hydrogen bond donors. The FDES formulation demonstrated significantly higher solubility than the pure drug within the temperature range of 20 to 50°C. DSC and FTIR characterization confirmed the formation of intermolecular interactions between the drug and the deep eutectic solvent components. The FDES formulation showed good stability after 60 days of storage at both 4°C and 25°C. This therapeutic deep eutectic solvent represents a novel liquid formulation approach for enhancing the solubility and bioavailability of fosamprenavir calcium, offering a promising alternative to conventional solid dosage forms.

Fig. 2 Experimentally data release kinetics in acetate buffer of FpnCa in powdered form and FpnCa–LA. (Prlić Kardum J.; et al. 2025)