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 nonradiolabelled 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(beta)) 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.