ANTI-BCL2 PHOSPHOROTHIOATE G3139 CLINICAL-PHARMACOLOGY - PLASMA-LEVELS DURING CONTINUOUS SUBCUTANEOUS INFUSION BY HPLC ASSAY

An HPLC assay has been developed to determine plasma levels of G3139 - a 18mer phosphorothioate oligonucleotide currently in Phase I clinica l studies. The assay utilizes anion exchange microchromatography, aque ous LiBr gradient elution, and UV absorbance detection. Minimum sensit ivity of approximately 0.2 mu g/ml plasma, or 35 nM of G3139, has been achieved. Analysis of preliminary clinical samples indicates subcutan eous infusion of G3139 at 2 mg/kg/day gives rise to steady state plasm a levels of 1-2 mu g/ml.