Pharmacokinetics and Safety of New NRTI Fosalvudine Tidoxil

The nucleoside analog alovudine (FLT) has been shown in prior studies to have potent anti-HIV activity, but also considerable toxicity. Fosalvudine tidoxil is a prodrug of alovudine (covalently linked with a lipid moiety) that may be significantly less toxic and remain at effective concentrations in the body for longer periods.

As reported at the XVI International AIDS Conference, held last week in Toronto, researchers from Argentina and the Netherlands conducted a study to determine whether the altered pharmacokinetic properties of fosalvudine make it less toxic and longer-lasting.

They presented data from a single-dose, open-label Phase-I study in which 24 antiretroviral-naive HIV positive participants received one of four oral doses of fosalvudine (5, 10, 20, or 40 mg).

Results

After 7 days of follow-up, no clinically significant clinical or laboratory adverse events occurred.

Fosalvudine became detectable in plasma 2 hours after intake of 5 mg and 1 hour after intake of 10, 20, or 40 mg.

Fosalvudine was still detectable in all patients in all dose groups 24 hours after intake.

The area under the curve (AUC), a measure of drug concentration, increased with increasing doses.

Conclusion

The researchers concluded that a single dose of 5-40 mg fosalvudine tidoxil "appears to be safe and well-tolerated." They added that, "The terminal half-life of fosalvudine tidoxil is short compared to the dosing interval. Clinically relevant accumulation of the pro-drug is not expected during multiple dosing." They said that a multiple-dose study would be conducted.

8/25/06

Reference
P Cahn, F Reuss, M Rolon. A phase I study to explore the safety, tolerability, and pharmacokinetics of Fosalvudine tidoxil in patients infected with HIV-1 XVI International AIDS Conference. Toronto, August 13-18, 2006. Abstract THLB0216.