Pharmacokinetics of tauromustine in cancer patients. Phase I studies.

The pharmacokinetic properties of tauromustine (TCNU) were studied in 31 cancer patients who participated in phase I trials. The patients received single oral doses of tauromustine in the range of 20-170 mg/m2. Plasma samples were taken over 24 h after administration and analysed for tauromustine by reversed-phase liquid chromatography. Parent TCNU could be demonstrated in the plasma of all patients. Its absorption was rapid (tmax = 38 +/- 22 min), the half-life was 57 +/- 22 min (mean +/- SD), and maximal concentration (Cmax) and AUC values were linearly related to the dose level. Thus, our study does not indicate dose-dependent pharmacokinetics for the drug in the range of 20-170 mg/m2. Thrombocytopenia was the dose-limiting toxicity of TCNU; the reduction of platelet counts appeared to be linearly related to the log dose and Cmax and AUC values. TCNU appears to exhibit pharmacokinetic properties that are different from those of other nitrosoureas, which might be important for the clinical effect of the drug.