Pharmacokinetics of 2-ethyl-1,3-hexanediol. I. Systemic disposition following single intravenous doses in male Fischer 344 rats.

A determination of the systemic pharmacokinetics of [1,3-14C]-2-ethyl-1,3-hexanediol (EHD) was conducted following i.v. dosing of male Fischer 344 rats. Pharmacokinetic analyses of the plasma data indicated that there is dose linearity in the 1.5 to 150 mg/kg range, and that EHD is cleared from plasma in a biexponential manner according to first order transfer and elimination processes. The data show that EHD-derived radioactivity is very rapidly distributed and then is slowly eliminated (probably as EHD metabolites) over a 48-hr period after a single i.v. injection. EHD is not found in the urine as unchanged test material by HPLC analysis following these i.v. doses, indicating that this chemical is probably completely metabolized in the rat. The appearance of EHD-derived radioactivity in the urine also follows a first order behavior, as evidenced by calculations of rate constants which are similar to the terminal rate constants from plasma radioactivity data. Both U infinity-Ut and dU/dt analyses of urine radioactivity data demonstrated that first order rate constants can be derived from urinary excretion data and supported the overall conclusion that the elimination of EHD from the rat follows first order processes in this range of i.v. doses.