Modulation of plasma thiols and mixed disulfides by BNP7787 in patients receiving paclitaxel/cisplatin therapy

摘要: BNP7787 (disodium 2,2′-dithio-bis-ethane sulfonate) was evaluated in a phase I clinical trial with paclitaxel and cisplatin to assess the safety potential efficacy for preventing or reducing cisplatin- paclitaxel-induced toxicities. During this effects of administration on total concentrations (oxidized plus free) cysteine, homocysteine GSH plasma, free WBC rate urinary excretion cysteine were studied. The pharmacokinetics ultrafilterable (free, non-protein bound) platinum also determined after (75 mg/m2) treatment which followed (175 mg/m2) (8.2 27.6 g/m2). Plasma thiols measured by HPLC fluorescence detection atomic absorption spectrophotometry. produced significant depletion all plasma patients Differences noted kinetics BNP7787-induced other thiols. A occurred time lag about 2 h end infusion, while reversible immediately following start thiol/disulfide nadir corresponding infusion. mean half-life 2.2 h, significantly longer than (0.23 h), (0.18 h; P 0.05). had no effect pharmacokinetics. 2-h most abundant thiol suggests that process may be related formation mesna from increased levels are not circulation until administration. No seen concentration WBC, possibly reflecting inability these cells take up BNP7787. results suggest has enhance antitumor activity depleting reactive plasma.