Absorption and disposition of cobalt naphthenate in rats after a single oral dose

The absorption and disposition of inorganic cobalt salts alter oral adminis tration have not been completely characterized. The objective of this proje ct was to investigate the absorption and disposition of cobalt naphthenate in Fischer 344 rats following a single oral dose. Cobalt naphthenate was gi ven orally at 3 doses: 0.333, 3.33, or 33.3 mg Co(II)/kg. Tissues, urine, a nd feces were collected over a 36-h period from the low- and high-dose grou ps; blood was collected from all 3 dose groups. The majority of the dose in both the low- and high-dose groups was excreted in the feces (42% and 73.1 %, respectively), indicating that cobalt was incompletely absorbed from the gastrointestinal tract following oral dosing. The percent of the dose excr eted in the urine was similar for low and high doses (31.8% and 26.3%, resp ectively). Cobalt concentrations were found to be highest in the liver and kidneys. The blood versus time cobalt concentration curves or the low-dose, intermediate-dose, and high-dose groups were elevated 4- to 5-fold, 14- to 25-fold, and 25- to 60-fold over control blood levels, respectively. The p eak plasma concentrations of 0.6 and 1.7 mu g Co(II)/ml occurred at approxi mately 4.3 h for the intermediate-dose group, and 3.3 h for the high-dose g roup. The terminal elimination half-lives were 24.7 and 24 h for the interm ediate- and high-dose groups, respectively. Thus, although the extent of co balt absorption as indicated by the blood concentrations and areas under th e blood-time curves was not proportional to dole, the calculated pharmacoki netic values for the time to peak blood concentration and the apparent elim ination rate constants were independent of dose. The amount excreted in the urine was also proportional to the dose. These apparent anomalies were not related to protein binding in blood.