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Tauromustine (TCNU) is an exploratory drug that has demonstrated activity in various solid tumors. We examined chromosome aberrations and plasma levels of the drug in two groups of patients receiving either a single dose of 130 mg/m or 40 mg/m on 3 consecutive days. Peak plasma concentrations (mean ±SD) were obtained at a similar time after both treatments, i.e., at 38±25, 32±24, 28±14, and 40±26 min after administration of 130 mg/m on day 1 and after that of 40 mg/m on days 1, 2, and 3, respectively. In addition, the cumulative area under the curve (AUC value) determined after administration of 40 mg/m×3 was similar to that noted after treatment with a single dose of 130 mg/m, i.e., 180 and 179 μg min ml, respectively. Both treatments induced chromosome aberrations (CAs) in peripheral blood lymphocytes. A dose-dependent increase in the number of CAs was found, with 40 mg/m producing 5.5% CAs and 130 mg/m yielding 20.9% CAs at 24 h after treatment. In addition, although the drug concentration declined to a level under the detection limit between the daily treatments, drug-induced chromosome damage was cumulative, with the 90-min values increasing from 4.8% on day 1 to 14.3% CAs on day 3. In individual patients, no correlation was found between CAs and kinetic parameters; however, the total mean CA yield was in agreement with the total drug exposure (CAs, 14.3% and 14.6%, AUC 180±62.8 and 179±115 μg min ml, respectively). [ABSTRACT FROM AUTHOR]

The stability of two nitrosoureas, tauromustine and lomustine, has been investigated in different media and buffers. All media tested, except Leibovitz’s L-15 medium, significantly increased the degradation rate of the investigated nitrosoureas at pH 7.4. Sodium bicarbonate seems to be the cause of the observed increase of the degradation rate, since it provides the main buffering capacity of all the media except for Leibovitz’s L-15 medium, which is based on phosphate buffer. Other ingredients in the media, such as amino acids, vitamins, and inorganic salts, or the ionic strength of a buffer, did not have any major effect on the degradation rate of the nitrosoureas. These results suggest that media containing carbonated buffer should be avoided when the anti-tumor effect of nitrosoureas is to be investigated in different cell cultures. [ABSTRACT FROM AUTHOR]