The aim of this work was to determine the pharmacokinetics of intravenous (iv) and intramuscular (im) ceftazidime administered to lactating (LTG; n = 6) and non-lactating (NLTG; n=6) healthy Creole goats in 2 trials (T1 and T2). During T1 and T2, goats randomly received a single dose of im or iv ceftazidime (10 mg/kg). Serum concentration of iv ceftazidime in NLTG and LTG goats is best described by 2 and 3 compartment models, respectively. The pharmacokinetic parameters of iv and im ceftazidime administered to LTG and NLTG showed statistically significant differences (P<0.05) in the constants (λz, T1 vs T2 [iv] 0.5±0.1 vs 0.3±0.1 /h; T1 vs T2 [im] 0.5±0.2 vs 0.3±0.1 /h) and in the mean times (t1/2, T 1 vs T 2 [iv] 1.6±0.3 vs 2.3±0.6 h; T 1 vs T 2 [im] 1.6±0.7 vs 2.6±0.9 h) of elimination. The bioavailability of ceftazidime in LTG and NLTG was 113.0 ± 17.8 and 96.0 ± 18.0 %, respectively. Ceftazidime concentration in milk at 2 h was: iv = 1.9 ± 0.2 and im = 2.4 ± 0.5 μg/m ; the penetration in milk was iv = 18.3 ± 13.5 and im = 14.3 ± 10.6 %. Ninety-six hours after iv and im administration, residues of the drug were not found in milk. In conclusion, ceftazidime, when administered to goats, showed high concentration times in serum, good penetration into milk and a bioavailability that makes it suitable to be used by the im route

Even though trifluralin ( α , α , α -2,6-dinitro-N-N-dipropyl-p-toluidine) is effective for the treatment of experimental Chagas disease, more preclinical toxicity studies need to be performed. Cell toxicity of trifluralin was studied in Hep-G2 and Vero C76 cells treated with 50 and 150 µ M trifluralin. The results show that duplication time, amount of cellular protein and cell protein/DNA values were normal. Histological, haematological and chemical parameters were measured in CF1 mice after oral trifluralin administration. Acute toxic effects were assayed by administration of 50 or 200 mg / kg body weight daily for 30 days, and chronic effects by administration of 200 mg / kg body weight once a week for 90 days (n = 20). In the acute scheme treatment, hepatic (glutamic-pyruvic, glutamic-oxalacetic and alkaline phosphatase activities; proteins and albumin plasma concentrations) and pancreatic (amylase, glycaemia) functions were normal. Mean corpuscular volume, haemoglobin and haematocrit decreased. Creatine phosphokinase, lactate dehydrogenase and glutamic-oxalacetic activity increased, suggesting lesion in myocardial tissue. Histology was normal, excepting for the heart (mild myocarditis). Similar results were observed in acutely treated animals. There were no differences in body weight gain for treated mice compared to controls. In view of the published therapeutic effects of trifluralin on CF1 Chagas disease model and considering the present results, trifluralin seems to be a moderately toxic drug with a potential selective effect on the myocardium.

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.

No abstract