The pharmacokinetics of pyrimethamine in the rat: effect of mefloquine.

The pharmacokinetics and tissue distribution of pyrimethamine have been determined in the rat. Following administration of pyrimethamine alone, drug concentrations declined biexponentially. By contrast, in the presence of mefloquine, the decline in pyrimethamine concentration more closely fitted a monoexponential pattern and the AUC0-6h for pyrimethamine was significantly reduced. Significantly more pyrimethamine was recovered from the livers but less from the lungs of the mefloquine-dosed rats compared with control. This study outlines a potentially clinically relevant drug interaction.