Pharmacokinetic modeling of saturable, renal resorption of perfluoroalkylacids in monkeys--probing the determinants of long plasma half-lives
Andersen, ME; Clewell, HJ; Tan, YM; Butenhoff, JL; Olsen, GW
HERO ID
818501
Reference Type
Journal Article
Year
2006
Language
English
PMID
| HERO ID | 818501 |
|---|---|
| In Press | No |
| Year | 2006 |
| Title | Pharmacokinetic modeling of saturable, renal resorption of perfluoroalkylacids in monkeys--probing the determinants of long plasma half-lives |
| Authors | Andersen, ME; Clewell, HJ; Tan, YM; Butenhoff, JL; Olsen, GW |
| Journal | Toxicology |
| Volume | 227 |
| Issue | 1-2 |
| Page Numbers | 156-164 |
| Abstract | Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) compounds associated with surface protection product manufactures are distributed globally. The 3-5-year half-lives, reproductive and liver toxicity in animals, and lack of understanding of the factors regulating retention in the body have led to a world-wide public concern for use of these materials. Using a novel physiologically-motivated pharmacokinetic model for renal clearance, perfluoroalkylacid pharmacokinetics in monkeys was successfully described by renal resorption via high efficiency transporters for both intravenous and oral dosing. Intravenous dosing with both PFOA and PFOS in Cynomolgus monkeys produced time course curves consistent with a two-compartment distribution. Extending the PK model for intravenous dosing to examine blood and urine time course data for repeated oral dosing clearly identified the saturable renal resorption. Resorption depends on kinetic factors for transport (T(mC), transport maximum; K(T), transport affinity) and free fraction in plasma (f(plasma)). For PFOA, these parameters were estimated to be 5mg/(h kg) (T(mC)), 0.055 mg/L (K(T)), and 0.02 (f(plasma)). PFOS has longer half-life and had respective values of 13.6 mg/(h kg), 0.023 mg/L, and 0.025. PFOS appeared to have a higher transport capacity and lower affinity than PFOA. Human kinetics indicates even higher resorption efficiency. |
| Doi | 10.1016/j.tox.2006.08.004 |
| Pmid | 16978759 |
| Wosid | WOS:000241258100016 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | Administration, Oral; Alkanesulfonic Acids/blood/pharmacokinetics/urine; Animals; Female; Fluorocarbons/blood/pharmacokinetics/urine; Half-Life; Injections, Intravenous; Kidney/metabolism; Macaca fascicularis; Male; Metabolic Clearance Rate; Models, Biological; Tissue Distribution; 0 (Alkanesulfonic Acids); 0 (Fluorocarbons); 1763-23-1 (perfluorooctane sulfonic acid); 307-34-6 (perfluorooctane) |
| Is Qa | No |