ON THE METABOLISM OF A NEW ANTISCHISTOSOME AGENTNITHIOCYAMINE

Metabolic studies of a new non-antimonial antischistosome agent-Nithiocyamine were carried out on animals and reviewed together with some human results. In rabbits, the blood concentration reached a peak at the 4th hour after oral administration, then fell gradually, pharmacokinetic parameters were assessed by the two compartment open model where three biological half-lives t_(1/2)ka, t_(1/2)α and t_(1/2)β were shown to be 0.855, 0.924 and 105.8 hours respectively; and the three rate constants k_el, k₂₁, and k₁₂, 0.0127, 0.398 and 0.356 hour^-1 respectively. The apparent volume of distribution (V_f)was calculated as 0.934L/kg.Nithiocyamine distributed widely in many tissues after absorption. In rats, at the 4th hour after oral administration, the drug occurred in the following tissues in concentrations of ascending order: the liver kidney, spleen, lung, muscle, heart, brain and blood. In infected rabbits, the schistosomes took up more drug than tissues of the host animal, and female schistosomes more than the male. Nithiocyamine was excreted only slowly through the urine and bile. Urinary excretion in human usually lasted more than 3 days after a single oral administration, and lasted more than 19 days after three consecutive dosages.The metabolites occurred in urine were extracted and separated by TLC, Chemical methods UV an. HPLC, examination revealed that it was the NCS group first reduced into amino, and then conjugated with glucuronic acid to form a N-glycoside.. This metabolic change is one of its biotransformation pathways.