The pharmacokinetics and metabolism of (1R, cis)- and (1R, trans)-tetramethrin in rats

1. The pharmacokinetics and metabolism of (1R, cis)- and (1R, trans)-isomers of tetramethrin (i.v. 0.25 mg/kg) were studied in rats. 2. The experimental data for the time course of the concentration of tetramethrin isomers in plasma fit a pharmacokinetic two-compartmental open model. Plasma levels of both isomers were similar. The terminal half-life of the trans-isomer in plasma was greater (125 min) than the cis-isomer (72 min). 3. The concentrations of the two metabolites, 3,4,5,6-tetrahydrophthalimide (TPI) and N-(hydroxymethyl)-3,4,5,6-tetrahydrophthalimide (MTI), were consistently higher in the plasma of rats treated with the trans-isomer than in those treated with the cis-isomer. 4. In rats treated with the trans-isomer, the majority of radioactivity excreted after 96 h was found in urine. The faeces was the major excretory route for rats treated with the cis-isomer (26% urine, 69% faeces with cis-isomer; 64% urine, 29% faeces with trans-isomer). 5. Metabolism of each isomer was rapid and complete. Parent chemical was not detected in urine and only small quantities of the intact cis-isomer were found in the faeces. MTI, TPI, and cyclohexane-1,2-dicarboximide (HPI) were detected in both urine and faeces. 6. The amount of radioactivity excreted into the bile was similar for both isomers. However, levels of the intact parent compound and TPI were higher in the bile isolated from rats treated with the trans-isomer. The trans-isomer was found to undergo enterohepatic circulation.