Pharmacokinetic behavior of enantiomeric pyrethroid esters in the cockroach, Periplaneta americana L

Abstract

The potent pyrethroid insecticide NRDC 157 ( I; 3-phenoxybenzyl (1 R, cis)-3 - (2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate) and its insecticidally inactive 1 S, cis enantiomer ( II) have similar cuticular penetration rates and are detectable in the hemolymph, nerve cord, fat body, and midgut of the American cockroach, Periplaneta americana, within 2 hr of topical application at 0.17 μg/g, a just-lethal dose of I. At this dose, both enantiomers show similar distribution patterns in these tissues, but symptoms of intoxication are seen only with I. Steady state concentrations of both enantiomers in the hemolymph and nerve cord are between 1.2 × 10 −7 and 1.7 × 10 −7 M. I and II are not detectably hydrolyzed by fat body, nerve cord, and hemolymph preparations and are not detectably oxidized by fat body preparations in vitro, but a very low oxidation rate is measured for II, but not I, in nerve cord preparations. These results do not demonstrate a pharmacokinetic basis for the difference in insecticidal activity between enantiomers and therefore it is likely that the site of pyrethroid action is stereospecific. The use of the inactive enantiomer II as a model to study the effects of dose on penetration and distribution in the absence of symptoms is explored.