Pharmacokinetics of Trifluralin in Blood and Heart Tissue of Mice

Abstract

Background: Trifluralin displays anti-Trypanosoma cruzi activity and a potential therapeutic effect for the treatment of Chagas disease. We assessed peroral and intramuscular trifluralin pharmacokinetics in mouse blood and heart tissue. Methods: A parallel experimental design was used. Healthy adult male CF1 albino mice (n = 108, 25–35 g bw) received a single peroral or intramuscular trifluralin dose (50 mg/kg in peanut oil). Blood and heart tissue samples were taken at set times after intramuscular and peroral trifluralin administration. Feces and tissue samples were taken 12 h after intramuscular trifluralin administration. Trifluralin concentrations in whole blood, feces and tissues were determined by HPLC. Results: After intramuscular and peroral administration, maximum whole blood concentration (C_max) was attained at 30 min and 2.0 h (t_max) (28.2 ± 0.7 and 7.8 ± 0.033 μg/ml; p < 0.05). C_max in heart tissue was attained at 1.0 and 2.0 h (0.6 ± 0.004 and 0.2 ± 0.002 μg/g; p < 0.05). Liver, perirenal and subcutaneous fat concentrations were 55.1, 66.3 and 59.7 ng/mg tissue protein. Peroral and intramuscular penetration ratios determined by comparing heart tissue areas under the curve were 6.3 and 4.0%, respectively. Conclusion: Intramuscular trifluralin could be a new alternative for the treatment of Chagas disease.

Chemoprophylactic Activity of Flubendazole in Cystic Echinococcosis

“…The characterization of the pharmacokinetic and/or pharmacodynamic patterns has been relevant to optimize drug use in the treatment of different bacterial and parasitic infections [9][10][11][12][13][14][15][16] . The assessment of the active drug exchange between plasma and peripheral tissues is now considered as an important predictor of in vivo drug efficacy.…”