Effects of the synergists piperonyl butoxide and S,S,S-tributyl phosphorotrithioate on propoxur pharmacokinetics in Blattella germanica (Blattodea : Blattellidae)

Effects of the synergists piperonyl butoxide (PBO) and S,S,S-tributyl phosp horotrithioate (DEF) on propoxur pharmacokinetics were examined in the Germ an cockroach, Blattella germanica (L.). Treatment of adult male German cock roaches with the cytochrome P450 monooxygenase inhibitor, PBO, or the ester ase inhibitor, DEF, increased propoxur toxicity by 2- and 6.8-fold, respect ively, implicating hydrolysis as a major detoxification route of propoxur i n the Gen-nan cockroach. However, significant hydrolytic metabolism could n ot be demonstrated conclusively in vitro resulting in a conflict between in situ bioassay data and in vitro metabolic studies. In vitro propoxur metab olism with NADPH-fortified microsomes produced at least nine metabolites. F ormation of metabolites was NADPH-dependent; no quantifiable metabolism was detected with cytosolic fractions. However, microsomal fractions lacking a n NADPH source did produce a low, but detectable, quantity of metabolites ( 1.6 pmol). PBO inhibited NADPH-dependent propoxur metabolism in a dose-depe ndent fashion, implicating cytochrome P450 monooxygenases as the enzyme sys tem responsible for the metabolism. Interestingly, DEF also inhibited the N ADPH-dependent metabolism of propoxur, albeit to a lower extent. Treatment with PBO or DEF also caused a significant reduction in the cuticular penetr ation rate of propoxur. The data demonstrate that unanticipated effects are possible with synergists and that caution must be exercised when interpret ing synergist results.