Absorption and disposition of cobalt naphthenate in rats after a single oral dose.
The absorption and disposition of inorganic cobalt salts after oral administration have not been completely characterized. The objective of this project was to investigate the absorption and disposition of cobalt naphthenate in Fischer 344 rats following a single oral dose. Cobalt naphthenate was given orally at 3 doses: 0.333, 3.33, or 33.3 mg Co(II)/kg. Tissues, urine, and feces were collected over a 36-h period from the low- and high-dose groups; 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 excreted in the urine was similar for low and high doses (31.8% and 26.3%, respectively). Cobalt concentrations were found to be highest in the liver and kidneys. The blood versus time cobalt concentration curves for 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 peak plasma concentrations of 0.6 and 1.7 microg Co(II)/ml occurred at approximately 4.3 h for the intermediate-dose group, and 3.3 h for the high-dose group. The terminal elimination half-lives were 24.7 and 24 h for the intermediate- and high-dose groups, respectively. Thus, although the extent of cobalt absorption as indicated by the blood concentrations and areas under the blood-time curves was not proportional to dose, the calculated pharmacokinetic values for the time to peak blood concentration and the apparent elimination 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.
Firriolo
J M
JM
Department of Pharmacology and Toxicology, Center for Toxicology, College of Pharmacy, University of Arizona, Tucson 85721, USA.
Ayala-Fierro
F
F
Sipes
I G
IG
Carter
D E
DE
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002264:Carboxylic Acids / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D003035:Cobalt / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000737:chemistry; D008297:Male; D011485:Protein Binding; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D001798:Blood Proteins; D002264:Carboxylic Acids; D003035:Cobalt; C046170:naphthenic acid