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Published in the Bulletin of Experimental Treatments for AIDS July 1998 issue, by the San Francisco AIDS Foundation. |
DRUG WATCH: FTC -- Antiretroviral in DevelopmentFTC is an antiviral nucleoside analog drug currently in development at Triangle Pharmaceuticals, located in Durham, NC. Structurally, FTC is similar to 3TC (Epivir), manufactured by Glaxo-Wellcome. However, in laboratory studies of anti-HIV activity, FTC appeared 3-10 times more potent than 3TC against HIV. Because of the similarities between the 2 drugs, including similar resistance patterns, people who are resistant to 3TC will gain no benefit from the new drug. Another feature of FTC is its activity against diverse strains of HIV. And, like 3TC, FTC is active against the hepatitis B virus (HBV). (Triangle Pharmaceuticals is also evaluating another licensed compound, L-FMAU, for the treatment of hepatitis B; L-FMAU looks promising in trials using the best available animal model, the woodchuck.) In pharmacokinetic studies (studies of the way the drug is absorbed by and cleared from the body) in animals, FTC was found to clear rapidly from the bloodstream at all doses studied. Oral bioavailability was considered good, and the drug was well tolerated. The only side effect noticed in mice was mild anemia, seen only at extremely high doses of 3,000 mg/kg/day. A Phase Ia study in humans evaluated the pharmacokinetics and safety of FTC in 12 people with HIV. Each participant took 6 single oral doses of FTC, ranging from 100 to 1200 mg, at 6-day intervals. Reportedly, all participants tolerated the drug well at all doses tested. FTC was found to be rapidly absorbed when taken in oral form, and cleared (excreted) primarily through urine. Food intake was found to cause a slight decrease in the rate of absorption, but overall oral bioavailability was strong and virtually unaffected by food. Also, absorption, metabolism and excretion were consistent from subject to subject. At the 5th Conference on Retroviruses and Opportunistic Infections in February, a late-breaker session featured a discussion of a small Phase I/II trial of FTC. In that trial, 10 people who had never before used either 3TC or abacavir took 1 of 2 doses of FTC as monotherapy (25 mg twice daily or 200 mg once daily) for 2 weeks. All participants had PCR tests for viral load to establish their pre- and post-treatment viral load levels. All 10 people experienced significant decreases in viral load. Those who took 25 mg twice daily had an average viral load decrease equal to a 1.4 log drop from an average baseline viral load of nearly 16,000 copies/mL. In the 200 mg dose group, the average decrease was 2.1 logs from an entry baseline viral load of 50,000 copies/mL. People taking the higher dose experienced immediate viral load decreases, while those on the lower dose first experienced reductions beginning on day 4 of the study. No significant side effects were reported at either level. FTC will likely be developed as a once-daily drug. Clinical trials are expected to begin this summer. Also this summer, at the 12th World AIDS Conference in Geneva, Switzerland, several poster presentations will discuss the most up-to-date findings and understanding of FTC. Leslie Hanna is Associate Editor of BETA.
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