On the search for new anticancer drugs 14: the plasma pharmacokinetics and tissue distribution of spin-labeled thio-TEPA (SL-O-TT)

• Published in: Cancer chemotherapy and pharmacology Vol. 15; no. 3; p. 185
• Main Authors: Gutierrez, P L, Cohen, B E, Sosnovsky, G, Davis, T A, Egorin, M J
• Format: Journal Article
• Language: English
• Published: Germany 01.01.1985
• Subjects: Animals; Chromatography, Gas; Electron Spin Resonance Spectroscopy; Half-Life; Kinetics; Male; Mice; Spin Labels - metabolism; Thiotepa - analogs & derivatives; Thiotepa - blood; Thiotepa - metabolism; Tissue Distribution
• ISSN: 0344-5704
• DOI: 10.1007/BF00263883

We defined the plasma and tissue concentrations and pharmacokinetics of SL-O-TT, a spin-labeled analog of thio-TEPA, in 35-44-g male Swiss Webster mice that had received spin-labeled thio-TEPA at a dosage of 10 mg/kg. Concentrations of spin-labeled thio-TEPA in ethyl acetate extracts of tissue and plasma were determined by gas-liquid chromatography and electron spin resonance spectroscopy. Plasma concentrations of spin-labeled thio-TEPA declined in a biexponential fashion that was well described by the equation: Ct = 21.5e-0.276t + 2.30e-0.026t indicating a half-life alpha of 2.5 min and a half-life beta of 26.6 min. After 2 h there was still spin-labeled thio-TE-PA in plasma, but not in tissues. In tissues, no spin-labeled thio-TEPA was detected with gas-liquid chromatography 15 min after injection, but with electron-spin resonance label was found in lung and skeletal muscle. The main metabolite of spin-labeled thio-TEPA is spin-labeled TEPA, where oxidative desulfurization is invoked as the main metabolic mechanism. Reduction of the spin label to the hydroxylamine was also observed with time.