Abstract
Background: BNP7787 (disodium 2,2′-dithio-bis-ethane sulfonate) was evaluated in a phase I clinical trial with paclitaxel and cisplatin to assess the safety and potential efficacy for preventing or reducing cisplatinand paclitaxel-induced toxicities. During this trial the effects of BNP7787 administration on the total concentrations (oxidized plus free) of cysteine, homocysteine and GSH in plasma, free and total GSH in WBC and rate of urinary excretion of cysteine were studied. The pharmacokinetics of ultrafilterable (free, non-protein bound) platinum were also determined after cisplatin (75 mg/m2) treatment which followed paclitaxel (175 mg/m2) and BNP7787 (8.2 to 27.6 g/m2). Method: Plasma thiols were measured by HPLC with fluorescence detection and platinum was measured by atomic absorption spectrophotometry. Results: BNP7787 administration produced a significant depletion of all plasma thiols in all the patients studied. Differences were noted in the kinetics of BNP7787-induced depletion of cysteine and other thiols. A significant depletion of cysteine occurred with a time lag of about 2 h after the end of BNP7787 infusion, while a reversible depletion of GSH and homocysteine occurred immediately following the start of BNP7787 infusion, with the plasma thiol/disulfide nadir corresponding to the end of infusion. The mean half-life of cysteine depletion following BNP7787 administration was 2.2 h, significantly longer than for homocysteine (0.23 h), or GSH (0.18 h; P
Original language | English (US) |
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Pages (from-to) | 376-384 |
Number of pages | 9 |
Journal | Cancer Chemotherapy and Pharmacology |
Volume | 51 |
Issue number | 5 |
State | Published - May 1 2003 |
Externally published | Yes |
Keywords
- BNP7787
- Cysteine Homocysteine
- Disulfides
- Glutathione
- Thiols
ASJC Scopus subject areas
- Cancer Research
- Pharmacology
- Oncology