Salicylamide is metabolized in man by biotransformation to
salicylamide glucuronide,
salicylamide sulfate, and
gentisamide glucuronide. The metabolites are quantitatively and rapidly excreted in urine. Study of the metabolism of this
drug in volunteers during episodes of
pyrogen-induced
fever shows a significant reduction in the half-life (t(1/2)) of the excretion of the
drug metabolites. The proportion of the
drug transformed to its major metabolite,
salicylamide glucuronide, is significantly reduced by
fever, with concomitant increase in the proportion of one or both of the other metabolites. Thus, the pattern of urinary metabolites of
salicylamide is altered. The shortened t(1/2) of the metabolite excretion is probably due to increased hepatic and renal blood flow known to accompany
pyrogen-induced
fever. This concept was supported by the observation that when two subjects were placed in a high-temperature environmental chamber, a condition in which hepatic and renal blood flows are known to diminish, the t(1/2) of
salicylamide metabolite excretion actually increased. No simple explanation exists to explain the changed metabolite pattern noted during febrile periods. It is most likely to be due to complex interactions between the direct or indirect effects of the
pyrogens and the factors affecting the hepatic biotransformation of drugs.