A PHARMACOKINETIC EVALUATION OF C-14-LABELED AFOVIRSEN SODIUM IN PATIENTS WITH GENITAL WARTS

Afovirsen sodium is a 20-mer phosphorothioate oligonucleotide designed to be complementary to the messenger ribonucleic acid sequence for th e translation initiation codon of the E2 protein vital to replication of human papillomaviruses types 6 and 11. C-14-Labeled afovirsen was g iven as a single-dose intradermal injection in each of four warts of f ive patients to determine the time-dependent changes in concentration of intact afovirsen in genital warts and to determine the systemic abs orption and elimination of radiolabeled compound. Intact afovirsen in genital warts was determined by high pressure liquid chromatography an alysis of protease K digested extracts. Intact afovirsen was present i n wart tissue for at least 72 hours at concentrations several times in excess of the estimated minimal inhibitory concentration of 1 mu mol/ L. Absorption of radiolabeled afovirsen from the injection site was ra pid, with a peak plasma concentration achieved within 1 hour. Clearanc e of afovirsen was primarily attributable to slow metabolism, with abo ut 30% of the radiolabel eliminated as C-14-CO2 in expired air over a 6-day period after dosing. Radioactivity eliminated in urine represent ed metabolites of afovirsen. From the clinical pharmacokinetic data pr esented here and from previously published pharmacokinetic data in rat s, the disposition of afovirsen in humans appears to be relatively sim ilar to that in rats. These data suggest that once or twice weekly dos ing regimen in the clinic may be appropriate.