CONICET | Buscador de Institutos y Recursos Humanos

Trifluralin (á,á,á-2,6-dinitro-N-N-dipropyl-p-toluidine) presents anti-Trypanosoma cruzi activity and potential therapeutic effect for the treatment of Chagas disease. Pharmacokinetic studies are needed for future application in human beings. This study was undertaken to assess oral and intramuscular trifluralin pharmacokinetics in blood, as well as trifluralin penetration in mice tissue, especially heart. We used 108 healthy adult male CF1 albino mice (25-35 g body weight) that received a single oral or intramuscular trifluralin dose of 50 mg/kg in peanut oil. Mice tissues and blood samples were obtained at 0.08, 0.17, 0.25, 0.5, 1.0, 2.0, 4.0, 8.0 and 12 hr after trifluralin administration. Trifluralin concentrations were determined by HPLC and analysed by non-compartmental models. After intramuscular administration, the drug was rapidly absorbed (Ka= 3.4 h-1); maximum blood concentration (Cmax) of 28.2 µg/mL was attained at 0.5 hr (tmax), and the drug was eliminated with an elimination half-life (t1/2) of 1.2 hr. After oral trifluralin administration, Ka was 1.2 h, Cmax of 7.8 µg/ml was attained at 2 hr, and t1/2 was 1.2 hr. Following oral and intramuscular injection, half-life in heart tissue was the same (2.7 h), Cmax of 0.2 and 0.6 µg/ml was attained at 2.0 and 1.0 hr, respectively, and the penetration ratio into heart tissue was 6.3 and 4.0%, respectively. Finger-print infrared spectroscopic analyses demonstrated that trifluralin was not degraded by light exposure under our experimental conditions. Both trifluralin concentration and proportion of metabolites were higher in liver and feces. Perirrenal and subcutaneous adipose tissue as well cardiac and skeletal muscle exhibited important trifluralin concentrations. We conclude that trifluralin could be a new alternative drug for the treatment of Chagas disease that should be included in future pharmacological studies.