Effect of dose and repeated dosing on the disposition and metabolism of sodium Omadine reg-sign (Na pyrithione; NaOM)

NaOM is an antimicrobial used to preserve industrial fluids. 14C-NaOM was administered to male and female Sprague-Dawley rats at 0.5 mg/kg i.v., 0.5 mg/kg p.o., 0.5 mg/kg p.o. after NaOM at 0.5 mg/kg p.o. daily for 14 days, or at 25 mg/kg p.o. 14C was determined is serial blood samples, in urine and feces at intervals up to 96 hr and in tissues (not i.v.) at 96 hr. Urine was analyzed by HPLC. 14C-NaOM was well absorbed orally, ca. or >90% of the dose. Blood kinetics of 14C-NaOM equivalents were complex, with secondary peak concentrations, several rates of elimination and a terminal t1/2 of ca. 14 days. For all treatment groups 73-85% of the dose was excreted in urine and 3-12% in feces. Urinary excretion was somewhat less extensive and slower after repeated and high p.o. doses. Tissues and carcasses of orally treated rats contained 2-3% of the dose. Total recoveries were 85-95%. Of the 12 metabolites found in urine, the major metabolite, K, 47-67% of the dose, was identified as 2-pyridinethiol-1-oxide-S-glucuronide. Differences were found in relative amounts of metabolites excreted, between routes, doses, schedules and sexes, e.g. K decreased from 59-67% at the low p.o. dose to 41-49% at the repeated and high p.o. doses. These data show that some changes occurred in disposition and metabolism with repeated dosing and increased dose