Sparsomycin is a cytotoxic
drug exhibiting a broad spectrum of in vitro activity against murine
tumors and many tumor cell lines. It also appears to be a potent stimulator of the antitumor activity of
cisplatin against
L1210 leukemia in vivo. However, because of its toxicity, the antitumor activity of
sparsomycin on murine
tumors in vivo has been disappointing. The purpose of our study was to investigate the pharmacokinetics of this
drug as well as the possible mechanisms that produce
sparsomycin toxicity. Tests on beagle dogs revealed that about 60% of the
drug is eliminated by metabolic clearance, while 40% is eliminated by the kidneys. After a single bolus injection of 0.1 mg/kg
sparsomycin without
narcosis,
sparsomycin was eliminated with a t beta 1/2 of 0.6-0.7 h, the AUC being 0.32-0.38 mg.h.l-1, and the volume of distribution (Vd) 0.26 l/kg. In addition to being subject to glomerular filtration,
sparsomycin is probably also actively excreted and actively reabsorbed by the renal tubuli.
Sparsomycin itself may inhibit its active tubular excretion, thus resulting in a decrease in the
drug's renal clearance and its accumulation in the plasma.
Sparsomycin appeared to be toxic primarily in the liver, disturbing its function and the synthesis of
plasma proteins. Two out of five dogs developed
hemorrhagic diathesis due to hypofibrinogenemia and deficiency of other
blood-coagulation factors.
Sparsomycin was not toxic to the bone marrow.