Cardiorespiratory depression and haemolysis due to thioridazine overdose in the rat

The cardiovascular and respiratory effects of an intravenous overdose of thioridazine (125 mg kg-1 h-1) were examined in either spontaneously breathing or artificially ventilated urethane-anaesthetized rats. In both groups PO2, heart rate and mean arterial pressure decreased and atrioventricular and intraventricular conduction time, as well as QT time, increased similarly. PCO2 and pH did not differ significantly except in spontaneously breathing rats where a severe acidosis occurred at the end of the experiments. Haemolysis was suspected. The same dose was administered intravenously to artificially ventilated rats. Plasma concentrations of the drug and its main metabolites, haematocrit and free plasma Hb were determined in separate groups. A severe haemolysis was observed. Thioridazine administered in the same doses intragastrically, intraduodenally or intraperitoneally resulted in lower plasma values than after intravenous administration and there was no haemolysis. Much higher oral doses produced haemolysis at 36 h, at which time plasma concentrations were not higher than those recorded after administration via the other non-intravenous routes. It is probable that the observed changes in cardiovascular and respiratory parameters are partly the result of haemolysis following thioridazine administration.