Chromosome aberrations and pharmacokinetics in patients receiving tauromustine as either a single or a repeated dose

• Published in: Cancer chemotherapy and pharmacology 1996, Vol.38 (4), p.309-316
• Main Authors: HARTLEY-ASP, B, HANSSON, K, VIBE-PETERSEN, J, HANSEN, H. H, POLACEK, J, ELLMAN, M, GUNNARSSON, P. O
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Biological and medical sciences; Chromosome Aberrations; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug toxicity and drugs side effects treatment; Humans; Lung Neoplasms - blood; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Nitrosourea Compounds - administration & dosage; Nitrosourea Compounds - adverse effects; Nitrosourea Compounds - pharmacokinetics; Pharmacology. Drug treatments; Taurine - administration & dosage; Taurine - adverse effects; Taurine - analogs & derivatives; Taurine - pharmacokinetics
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s002800050488

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/m2 or 40 mg/m2 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/m2 on day 1 and after that of 40 mg/m2 on days 1, 2, and 3, respectively. In addition, the cumulative area under the curve (AUC value) determined after administration of 40 mg/m2 x 3 was similar to that noted after treatment with a single dose of 130 mg/m2, i.e., 180 and 179 micrograms min ml-1, 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/m2 producing 5.5% CAs and 130 mg/m2 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 micrograms min ml-1, respectively.