Pharmacokinetics of fenvalerate after intravenous administration to sheep

The pharmacokinetics of total radioactivity and of intact fenvalerate were determined in sheep treated intravenously with radiolabelled or non-radiolabelled fenvalerate. Mean residence times (MRT) of total radioactivity and intact fenvalerate in plasma were 910 (±75) and 39 (±3) min, while harmonic mean elimination-phase half-lives (TM_β) were 990 and 82 min, each respectively. Systemic clearance values (Cl_S) of total radioactivity and intact fenvalerate were 2·8 (±0·3) ml min^?1 kg^?1 and 51·3 (±5·9) ml min^?1 kg^?1, respectively. Volumes of distribution at steady state (V_SS) were each near 2500 ml kg^?1. Elimination of radioactivity occurred, in part (33·3 (±3·3)% of dose), by renal excretion, at a rate (0·9 (±0·1) ml min^?1 kg^?1), similar to that of glomerular filtration. These data are consistent with a disposition model according to which intact fenvalerate was rapidly distributed into a peripheral compartment, where metabolism occurred. In addition, since the elimination half-life of fenvalerate from plasma was less than 90 min after intravenous injection, ‘flip-flop’ kinetics should be considered when longer elimination half-lives are observed after oral or dermal exposures.