Pharmacokinetics of cis- and trans-substituted pyrethroids in the American cockroach☆

Abstract The pharmacokinetic behavior of cis and trans isomers of pyrethroids after topical application to adult male American cockroaches ( Periplaneta americana L.) was examined using the insecticidal 1R,cis (NRDC 157; I ) and 1R,trans (NRDC 163; III ) isomers of 3-phenoxybenzyl 3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate and their insecticidally inactive 1S,cis ( II ) and 1S,trans ( IV ) enantiomers. III was detected in the hemolymph, nerve cord, and fat body of animals receiving a just-lethal dose (0.6 μg/g) within 2 hr after topical application. The pattern of accumulation of III was similar to that previously determined for I at a just-lethal dose, but quantitative comparisons revealed that the cis isomer I was delivered from the site of application to the nerve cord eightfold more efficiently than III . The inactive enantiomers II and IV were administered at the same dose (0.60 μg/g) to compare the rates of cuticular penetration and in vivo degradation of cis and trans isomers in the absence of intoxication symptoms. II penetrated somewhat more rapidly than IV and achieved higher levels in whole body extracts, but there was no difference between isomers in the rates of overall degradation of applied pyrethroid. These studies demonstrated a twofold difference in internal availability, but they did not reveal sufficient pharmacokinetic selectivity to explain the large difference in the access of I and III to the nerve cord observed in the tissue uptake studies. III was hydrolyzed by nerve cord homogenates in vitro at a rate 5 times greater than that of I , but neither ester underwent detectable oxidative metabolism in this system. Local selective metabolism by the nerve cord is suggested as an important determinant of the levels of parent pyrethroid found in this tissue. These results demonstrate the significance of pharmacokinetic selectivity in determining the relative access of topically applied cis - and trans -substituted pyrethroids to the insect nervous system.