Metabolism of metofluthrin in rats: II. Excretion, distribution and amount of metabolites

Abstract

1. ¹⁴C-Labelled E/Z isomers of a synthetic pyrethroid metofluthrin ((E/Z)-(1 R,3 R)-2,3,5,6-tetrafluoro-4-(methoxymethyl)benzyl 2,2-dimethyl-3-(1-propenyl)-cyclopropanecarboxylate, abbreviated as RTE/RTZ, respectively) were used for rat metabolism studies. ¹⁴C-RTE or RTZ labelled at the carbonyl-carbon [acid-¹⁴C] or the methoxymethylbenzyl-α-carbon [alcohol-¹⁴C] was administered orally to rats at 1 and 20 mg/kg.

2. Dosed compounds were mostly absorbed, metabolised, and rapidly excreted. Dose-related increase in blood AUC suggested no saturation of absorption at the high dose. Blood ¹⁴C was maximal at 3–8 h and decreased with a half-life of 52–163 h. Radioactivity in tissues, blood and plasma decreased basically at the same rate and the sum fell below 0.2% of the dose at 168 h.

3. Although the major metabolic pathways of the isomers, that is, ester cleavage, O-demethylation and ω-oxidation, were similar, there was a notable difference. The RTZ double bond commonly undergoes epoxidation while RTE double bond mainly undergoes glutathione conjugation, which causes faster elimination from plasma and greater excretion into faeces on RTE. Faster urinary excretion and elimination from blood were observed for the alcohol moiety than the acid moiety.

4. In conclusion, this study described the overall metabolic profiles of metofluthrin and identified the differences in metabolic breakdown between the isomers. No marked sex-/dose-related differences were observed.

Keywords:

• ADME
• eminence
• metofluthrin
• pyrethroid
• rat
• SumiOne

Declaration of interest

All in-life and analytical phases described in this article were conducted in LSI Medience Corporation and were sponsored by Sumitomo Chemical Co., Ltd. The authors have no other conflicts of interest directly relevant to the content of this article.

Supplementary material available online