Summary
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.
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References
Caddy B, Idowu OR, Stuart JF (1982) A high pressure liquid chromatographic procedure for monitoring 1-(2-chloroethyl)-3-(4-trans-methylcyclohexyl)-1-nitrosourea levels in body fluids. Ther Drug Monit 4: 389
Hartley-Asp B, Christensson P-I, Gunnarsson K, Gunnarsson PO, Polacek J, Stamvik A (1988) Anti-tumour, toxicological and pharmacokinetic properties of a novel taurine-based nitrosourea (TCNU). Invest New Drugs 6: 35
Lee FYF, Workman P, Roberts JT, Bleehen NM (1985) Clinical pharmacokinetics of oral CCNU (Lomustine). Cancer Chemother Pharmacol 14: 125
Lemoine R, Gouyette A (1979) Stability and preliminary pharmacokinetic studies of 1-(2-chloroethyl)-3-[1-(5′-paranitrobenzoyl-2′-3′-isopropylidene)-α,β-D-ribofuranosyl]-1-nitrosourea (RFCNU), a nonimmunosuppressive nitrosourea. Cancer Treat Rep 63: 1335
Polacek J, Gunnarsson PO, Brandin S (1988) Determination of tauromustine, a nitrosourea-based antitumour agent, in plasma by high-performance liquid chromatography. J Chromatogr 425: 424
Pratesi G, Savi G (1988) Effects of tauromustine, a water soluble nitrosourea compound, on NMU-1 murine lung tumor. Anticancer Drug Des (submitted)
Roed H, Vindelöv LL, Sprang-Thomsen M, Christensen IJ, Hansen HH (1987) In vitro evaluation of a new nitrosourea, TCNU, against human small cell lung cancer cell lines. Cancer Chemother Pharmacol 19: 315
Schulze-Delrieu K (1979) Metoclopramide. Gastroenterology 77: 768
Smyth JF, Macpherson JS, Warrington PS, Kerr ME, Whelan JM, Cornblett MA, Leonard RCF (1987) Phase I study of TCNU, a novel nitrosourea. Eur J Clin Oncol 23: 1815
Vibe-Petersen J, Bork E, Möller H, Hansen HH (1987) A phase I clinical evaluation of 1-(2-chloroethyl)3-[2-(dimethylaminosulphonyl) ethyl]-1-nitrosourea (TCNU). Eur J Clin Oncol 23: 1837
Weinkam RJ, Lin HS (1982) Chloroethylnitrosourea cancer chemotherapeutic agents. Adv Pharmacol Chemother 19: 1
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Gunnarsson, P.O., Vibe-Petersen, J., Macpherson, J.S. et al. Pharmacokinetics of tauromustine in cancer patients. Cancer Chemother. Pharmacol. 23, 176–180 (1989). https://doi.org/10.1007/BF00267951
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DOI: https://doi.org/10.1007/BF00267951