Biodistribution and excretion of radioactivity after the administration of 166Ho-chitosan complex (DW-166HC) into the prostate of rat.

PURPOSE: The objective of this study was to determine the fate of the 166Ho-chitosan complex (DW-166HC) in rats by examining its absorption, distribution and excretion after administration into the prostate. METHODS: About 100 microCi of DW-166HC [containing 0.1875 mg of Ho(NO3)3.5H2O and 0.25 mg of chitosan] was administered intraprostatically. The level of radioactivity in blood, urinary and faecal excretion, and radioactivity distribution were examined. To determine the effect of chitosan in DW-166HC, 166Ho nitrate alone [0.1875 mg of Ho(NO3)3.5H2O] was administered into the prostate of male rats, and radioactivity distribution was examined using whole-body autoradiography. RESULTS: After administration of DW-166HC into the prostate, cumulative urinary and faecal excretion over the period 0-72 h was 0.35% and 0.11%, respectively. The radioactivity at the administration site was extremely high at all time points up to 144 h (>98% of injected dose). The small amount of radioactivity which did transfer from the administration site distributed mainly to the liver, spleen, kidney cortex and bone. Compared with the DW-166HC group, the group that received 166Ho nitrate alone displayed three- to fourfold higher levels of radioactivity in the main tissues, including liver, spleen, kidney cortex and bone, at 24 h after administration (P < 0.05). CONCLUSION: The results of this study show clearly that most of the administered DW-166HC remained at the administration site. It is concluded that the chitosan complex may be used to retain 166Ho within a limited area in cancer of the prostate.

Metabolism and disposition of novel des-fluoro quinolone garenoxacin in experimental animals and an interspecies scaling of pharmacokinetic parameters.

Garenoxacin is a novel quinolone that does not have a fluorine substituent at the C-6 position in the quinoline ring. Garenoxacin or 14C-garenoxacin was intravenously or orally administered to rats, dogs, and monkeys. Metabolic profiles and pharmacokinetic parameters were investigated focusing on the species differences and the allometric scaling of pharmacokinetic parameters. Garenoxacin was well absorbed following oral administration then underwent phase II metabolism in all species tested. Major metabolites of garenoxacin were the sulfate of garenoxacin (M1) and glucuronide (M6). Oxidative metabolites were present in very minor concentrations in all species tested. Another minor route of metabolism was the formation of the carbamoyl glucuronide. Garenoxacin is characterized across species by the observation that it circulates systemically, is excreted renally as unchanged drug, and is metabolized to M1 and M6, which are excreted specifically into the bile. The total clearances (CL) were 12.1, 2.43, and 3.39 ml/min/kg for rats, dogs, and monkeys, respectively. The distribution volume values of garenoxacin (Vss) were 0.88, 1.29, and 0.96 l/kg for rats, dogs, and monkeys, respectively. In all animals tested, the extrarenal clearance was larger than the renal clearance, and neither of the clearances was limited by blood flow. Despite these conditions, garenoxacin showed a good correlation for CL and Vss for allometric interspecies scaling.