Doxazosin and the metabolism of aminopyrine in perfused rat liver

The effects of doxazosin, an α-adrenergic blocking agent, on aminopyrine metabolism were examined in a recirculating perfused rat liver. The results showed that doxazosin (5 mg kg^-1 b.w., i.p. for 14 days) did not stimulate the rate of aminopyrine metabolism, whereas phenobarbital (75 mg kg^-1 b.w., i.p. for 7 days) showed a typical behaviour of an inducer. Doxazosin (10 mg kg^-1 b.w., i.p. and 1 μg ml^-1 in perfusion medium) did not inhibit aminopyrine metabolism, while cimetidine (120 mg kg^-1 b.w., i.p. and 10 μg ml^-1 in perfusion medium) inhibited it. There was no difference in GPT concentrations in serum and perfusion medium at the beginning and end of the perfusion procedure and that all liver groups were viable at the end of perfusion as shown by the absence of trypan blue uptake. It may be concluded that doxazosin does not influence the activity of liver cytochrome P450 in the rat.