Anand_2006_Drug.Metab.Dispos_34_389

Deltamethrin (DLM) is a relatively potent and widely used pyrethroid insecticide. Inefficient detoxification has been proposed to be the primary reason for the greater sensitivity of immature rats to the acute neurotoxicity of DLM. The objective of this study was to test this hypothesis by characterizing the age dependence of DLM metabolism in vitro, as well as toxic signs and blood levels of the neurotoxic parent compound following administration of 10 mg DLM/kg p.o. in glycerol formal. Metabolism was quantified in vitro by monitoring the disappearance of the parent compound from plasma [via carboxylesterases (CaEs)] and liver microsomes [via CaEs and cytochromes P450 (P450s)] obtained from 10-, 21-, and 40-day-old male Sprague-Dawley rats. Mean (+/-S.E.) intrinsic clearances (Vmax/Km) in these respective age groups by liver P450s (4.99+/-0.32, 16.99+/-1.85, and 38.45+/-7.03) and by liver CaEs (0.34+/-0.05, 1.77+/-0.38, and 2.53+/-0.19) and plasma CaEs (0.39+/-0.06, 0.80+/-0.09, and 2.28+/-0.56) increased significantly (p