PHARMACOKINETICS OF AN ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS ANTISENSE OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATE (GEM-91) IN HIV-INFECTED SUBJECTS

Human pharmacokinetics of an antisense oligodeoxynucleotide phosphorot hioate (GEM 91) developed as an anti-human immunodeficiency virus (HIV ) agent was carried out in this study, S-35-Labeled GEM 91 was adminis tered to six HIV-infected individuals by means of 2-hour intravenous i nfusions at a dose of 0.1 mg/kg, Plasma disappearance curves for GEM 9 1-derived radioactivity could be described by the sum of two exponenti als, with half-life values of 0.18 +/- 0.04 and 26.71 +/- 1.67 hours, The radioactivity in plasma was further evaluated by polyacrylamide ge l electrophoresis, showing the presence of both intact GEM 91 and lowe r molecular weight metabolites, Urinary excretion represented the majo r pathway of elimination, with 49.15% +/- 6.80% of the administered do se excreted within 24 hours and 70.37% +/- 6.72% over 96 hours after d osing, The radioactivity in urine was associated with fewer molecular weight metabolites, No drug-related toxicity was observed.