Metabolism of 2,6-Dichloro-4-(3,3-dichloroallyloxy)phenyl 3-[5-(trifluoromethyl)-2-pyridyloxy]propyl Ether (Pyridalyl) in Rats after Repeated Oral Administration and a Simple Physiologically Based Pharmacokinetic Modeling in Brown and White Adipose Tissues

Abstract

in perirenal adipose tissue and lungs was pyridalyl, accounting for greater than 90 and 60%, respectively, of the total, whereas a major metabolite in whole blood, kidneys, and liver was a dehalogenated metabolite. The experimental data were simulated with simple physiologically based pharmacokinetics using fourcompartment models with assumption of lymphatic absorption and membrane permeability in adipose tissues. The different kinetics in brown and white adipose tissues was reasonably predicted in this model, with large distribution volume in adipose tissues and high hepatic clearance in liver. Sex-related difference of pyridalyl concentration in liver was considered to be a result of different unbound fraction times the hepatic intrinsic clearance (f ؋ CL int ) of 1.8 and 12 l/h for male and female, respectively.

Depressive-like behavior induced by tumor necrosis factor-α is attenuated by m-trifluoromethyl-diphenyl diselenide in mice

“…In addition, (m-CF 3 -PhSe) 2 is a lipophilic compound and the effect of low doses in the subchronic treatment could be due an accumulation process. Lipophilic compounds are known to accumulate in adipose tissue and to be eliminated slowly (Nagahori et al, 2010). Lastly, it is not possible to affirm if the antidepressant-like effect of (m-CF 3 -PhSe) 2 in this experimental model is due to an immunoregulatory action of this compound or the already demonstrated effects of (m-CF 3 -PhSe) 2 in the serotonergic system.…”

Qualitative and quantitative determinations of pyridalyl and metabolites in excrement of two representative Lepidoptera pests

“…15,16 Related research has focused more on the physiological and biological safety of pyridalyl. 9,[17][18][19][20] For instance, mammals and insects, e.g. rats and Chironomus yoshimatsui are usually employed as experimental organisms.…”

“…In related reports, thin layer chromatography as well as twodimensional gel electrophoresis has been widely employed to prepare samples, 22,23 and metabolites are conventionally determined by isotope-labeled strategies. 7,18,21,24 Both strategies in sample preparation would generally be accompanied with a lot of sample consumption, experimental time and labor work. Moreover, strict safety regulations and chemical treatments were conventionally required in isotope-labeled methods.…”