Therapeutic Nifurtimox and Benznidazole monitoring in blood

BULFFER, R.F.; FANELLI, S.L; CASTRO, J. A.

Rosario, Santa Fe

Congreso; 41a Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE; 2009

Sociedad Argentina de Farmacología Experimental (SAFE)

There are two drugs accepted for the etiological treatment of Chagas´disease, Nifurtimox (Nfx) and Benznidazole (Bz). Both have serious toxic side effects so it is necessary to have an appropriate methodology for their therapeutic monitoring. In this study we analyzed the use of HPLC and UV-Visible methods for the drugs determination in blood. Animals were given a single intragastric dose of Bz or Nfx (100 mg/kg in 1 % carboxymethylcellulose). Rats were killed at different times (1h, 3h, 6h or 24h). Blood samples were extracted with dichloromethane in ExtrelutÒ columns. The solvent was evaporated to dryness under nitrogen and the extracts were further analyzed by HPLC (C18 ODS Hypersil column, 20 cm x 2.1 mm ID, 5 µm particle size and diode array detector) or in an Spectrophotometer Shimadzu 2550 at 320 nm (Bz) or 400 nm (Nfx). The efficiency of recovery of Bz or Nfx added to blood were 90.6 % and 52 % respectively. Plots of peak areas against concentration were linear over the concentration ranges studied. Maximum blood level was found after 3 h of treatment for both antichagasic, while after 24 h of treatment the drugs were no detected. Although HPLC-UV method was more sensitive, both methodologies would be applicable for therapeutic monitoring according to instruments availability.