Abstract
Pharmacokinetics in plasma and blood cells concentrations, tissue distribution and excretion of amrubicin hydrochloride (SM-5887), a novel antitumor agent, were investigated after a single intravenous administration of 14C-labeled SM-5887 at a dose of 1.5 mg/kg to dogs.
1. The radioactivity levels in plasma and blood cells decreased multi-exponentially, and the levels of radioactivity in blood cells were 1/2-1/3 of those in plasma.
2. The concentrations of the unchanged SM-5887 in plasma and blood cells decreased more rapidly than total radioactivity. The α- and β-phase half lives of SM-5887 concentration in plasma were 20 min and 3.8 hr, respectively. Plasma and blood cell concentrations of amrubicinol (SM-5887-13-OH), the major bioactive metabolite, increased rapidly, and then decreased slowly. Other aglycone metabolites without the sugar moiety were also detected in plasma and blood cells.
3. The radioactivity in each tissue reached a maximum concentration at 1 or 4 hr after administration. The radioactivity levels were relatively high in most tissues including liver, gallbladder, kidney, lung, spleen, pancreas and prostate gland. The radioactivity in most tissues disappeared gradually with a profile similar to that in plasma, except few tissues such as liver, eye, pigmented skin and testis. In liver, 9 % of the dosed radioactivity was observed at 168 hr after administration.
4. The major metabolites in tissues were Met B and SM-5887-13-OH. The concentration of SM-5887 in tissues were low, and decreased rapidly.
5. Within 168 hr after administration, 8 % and 74% of the dosed radioactivity were excreted into urine and feces, respectively.
