COMPARATIVE PHARMACOKINETICS OF PERFLUOROHEXANESULFONATE (PFHxS) IN RATS AND MONKEYS

摘要

Perfluorohexanesulfonate (PFHxS) has been found in biological samples from wildlife and humans. The geometric mean half-life of serum elimination of PFHxS in humans has been estimated to be 7.3 years (95% CI 5.8-9.2 years). We undertook a series of studies to establish pharmacokinetic parameters in non-human species. Male (M) and female (F) monkeys were given a single intravenous (IV) dose of K+PFHxS and serum and urine PFHxS concentrations were followed for 171 d. M and F rats were given single oral doses of 1, 10, or 100 mg/kg K+PFHxS and urine and feces were collected over 96 h and serum and liver collected at 96 h. Jugularcannulated M and F rats were given either IV or oral single 10 mg/kg doses of K+PFHxS and serum concentrations of PFHxS were followed for 24 h. M and F rats were given a single IV dose of 10 mg/kg, and serum, feces, and urine were collected weekly for 10 weeks. All PFHxS analyses utilized LC-MSMS methods. Pharmacokinetic parameters were determined by WinNonlin?software. Volumes of distribution indicated predominant extracellular distribution. Mean serum elimination half-lives were 141 and 87 d for M and F monkeys and ca. 30 and 1.5 d for M and F rats.