Relations between hepatotoxicity and pharmacokinetics of paracetamol in rats and mice

A dose-dependent increase of paracetamol serum half-life (t1/2) was found after oral and intravenous application in rats and oral application in mice. The hepatotoxic effects of paracetamol were not correlated with this prolongation of t1/2. Dithiocarb protected rats against paracetamol liver damage but did not change paracetamol t1/2. Paracetamol t1/2 was not influenced either by a hepatotoxic dose of carbon tetrachloride. In conclusion, the dose-dependent prolongation of paracetamol serum half-life is not due to paracetamol-induced liver damage but merely the consequence of saturated elimination processes.