Influence of phenacetin and its metabolites on renal function

To investigate the pathogenesis of phenacetin-induced nephropathy, the influence of aspirin and caffeine on phenacetin metabolism was studied. Eight healthy male volunteers participated in the study after giving written consent. They were randomly divided into 2 groups. Phenacetin was given to one group, and phenacetin, aspirin and caffeine were given to the other group based on a cross-over design. Blood and urine were collected over a period of 24 hours. The urinary excretion and plasma concentrations of unchanged phenacetin, acetaminophen, acetaminophen glucuronide and acetaminophen sulphate were measured by high performance liquid chromatography. The proportions of urinary excretion of these substances were not significantly different in the two groups. The pharmacokinetic parameters of these substances were also fundamentally identical. It may be concluded that aspirin and caffeine do not alter the phenacetin metabolism. However, other minor metabolites such as p-phenetidine must be closely investigated before we can draw any final conclusions.