Plasma pharmacokinetics and tissue distribution of thiotepa in mice

We defined the plasma and tissue concentrations and pharmacokinetics of thiotepa in 22.8-29.3-g male Swiss-Webster mice injected iv with thiotepa at a dose of 5 mg/kg. Concentrations of thiotepa in ethyl acetate extracts of tissue and plasma were determined by gas chromatography. Plasma concentrations of thiotepa declined in a biexponential fashion that was well-described by the equation: Ct = 52.03e-3.36t + 3.10e-0.072t, indicating an alpha-half-life of 0.21 mins and a beta-half-life of 9.62 mins. Thiotepa was rapidly and extensively distributed through the tissues studied and was not concentrated in any particular tissue, although the liver consistently contained concentrations of thiotepa much lower than any other tissue studied. By 1 hr after injection, there was little thiotepa in plasma or any tissue.