Oltipraz concentrations in plasma, buccal mucosa cells, and lipids: Pharmacological studies

Oltipraz is considered one of the most potent cancer chemoprevention agents , as shown in preclinical studies. Its pharmacological effects in humans ha ve been associated with unusual toxicity affecting the fingers and toes. Th is study was designed to test intermittent dosing schedules using two dosag e levels: 500 mg as a single weekly dose and 200 mg as a biweekly dose, eac h for 30 days. Fifteen men and women were studied in each dosing group. All were heavy smokers considered to be at high risk for developing lung cance r, Plasma, buccal mucosa cell, and lipoprotein concentrations were measured at different intervals corresponding to the time period when most of the a dverse effects occur, No serious toxicities were observed using these doses and schedules, The plasma and buccal mucosa cell concentrations of Oltipra z showed substantial interindividual variations at each sampling. Some subj ects had no detectable plasma or buccal mucosal cell Oltipraz concentration s. The distribution of Oltipraz incorporation into the lipid fractions and albumin was changed by the administration of different schedules of Oltipra z, The results of this study suggest that the intermittent dosing is well t olerated and does not result in steady state in plasma or buccal mucosa cel ls. The variation and lack of detectable Oltipraz concentration in plasma, buccal mucosa cells, and lipids may affect both the toxicity and the pharma cological effects when these doses and schedules are used.