Abstract
Blood and plasma concentrations, metabolism and excretion were investigated in male dogs after a single intravenous administration of [14C] TZU.
1. Blood concentration of radioactivity decreased gradually until 2 hr after dosing, and then declined rapidly until 12 hr, followed by the decrease with halflife of 7.34 hr. The time-profile of radioactivity in the plasma was similar to that of the blood.
2. Three metabolites, M-1, M-2 and M-3 were simultaneously determined by LC/MS-SIM in dog plasma and urine.
3. Plasma concentration of M-1 reached the Cmax of 15.0 nmol/ml at 10 min after dosing and declined biphasically with half-lives of 0.22 hr (T1/2α) and 1.71 hr (T1/2β). Finally it decreased below the detection limit at 24 hr. M-2 reached the Cmax of 2.8 nmol/ml at 2 hr and declined biphasically with respective halflives of 1.93 hr (T1/2α) and 6.77 hr (T1/2β). M-3 reached the Cmax of 0.5 nmol/ml at 2 hr and declined with half-life of 3.05 hr.
4. The excretions of radioactivity in urine and feces were 71.9% and 15.1% of dose within 24 hr after administration, respectively. 98.4% of administered radioactivity was excreted in urine and feces within 168 hr.
5. The amount of M-3 in the urine after hydrolysis with β-glucuronidase and arylsulfatase was 4 times higher than that before hydrolysis. It indicated that M-3 was almost excreted into urine as glucuronide and/or sulfate. On the other hand, M-1 and M-2 were excreted in urine in unconjugated form.
6. 50% and 60% of radioactivity in dog plasma and urine were composed of three metabolites (M-1, M-2 and M-3) determined by LC/MS-SIM.
