Tissue distribution and excretion of ^(125)I-lidamycin in mice and rats

AIM: To investigate the tissue distribution, urinary and fecal excretions of 125I-lidamycin (125I-C-1027) in mice and its biliary excretion in rats. METHODS:The total radioactivity assay (RA method) and the radioactivity assay after precipitation with 200 mL/L trichloroacetic add (TCA-RA method) were used to dete-rmine the tissue distribution,and the urinary and fecal excretions of 125I-C-1027 in mice and its biliary excretion in rats. RESULTS:Tissue concentrations reached the peak at the fifth minute after administration of 125I-C-1027 to mice. The highest concentration was in kidney, and the lowest in brain at all test-time points. The organs of the concentrations of 125I-C-1027 from high to low were kidney, lung, liver, stomach, spleen, uterus, ovary, intestine, muscle, heart, testis, fat, and brain in mice. The accumulative excretion amounts of 0-24 h, and 0-96 h after administration of 125I-C-1027 were 68.36 and 71.64% in urine, and 2.60 and 3.21% in feces of mice, respectively, and the accumulative excretion amount of 0-24 h was 3.57% in bile in rats. CONCLUSION: Our results reflect the characteristics of the tissue distribution, urinary and fecal excretions of 125I-C-1027 in mice and the biliary excretion of 125I-C-1027 and its metabolites in rats, and indicate that 125I-C-1027 and its metabolites are mainly distributed in kidney, and excreted in urine.

Pharmacokinetics of C-1027 in mice as determined by TCA-RA method

AIM: To validate a radioactivity assay, the TCA-RA method, for the measurement of C-1027 in serum and to evaluate its application in determination of pharmacokinetics of C-1027 in mice. METHODS: 125I-C-1027 was prepared by the lodogen method and separated by HPLC. The radioactivity assay was established and used to determine 125I-C-1027 in mice at doses of 10, 50 and 100 μg/kg after precipitation with 20% trichloroacetic acid (TCA-RA method). Several pharmacokinetic parameters were determined after intravenous injection of 125I-C-1027 to mice. RESULTS: After intravenous injection of 125I-C-1027 to mice, at doses of 10, 50 and 100μg/kg; the apparent distribution volumes (Vd) were 0.26, 0.31 and 0.33 L/kg; the biological half-lives (T1/2) were 3.10, 3.40 and 3.90 h; the areas under curve (AUC) were 18.41, 103.69 and 202.74 ng/h/mL; the elimination rate constants (A) were 1.04, 1.26 and 0.58/h; and the total body clearance (Cl) were 0.54, 0.48 and 0.49 L/kg/h, respectively. CONCLUSION: TCA-RA is a sensitive, reliable and suitable method for the determination of 125I-C-1027 in mouse serum.