Absorption, biotransformation, and pharmacokinetics of salicylsalicylic acid in humans.

The absorption, biotransformation, and pharmacokinetics of the antiinflammatory drug salicylsalicylic acid (SSA) were studied. Healthy adult males received 1000 mg SSA and 1300 mg aspirin according to a crossover design either as a single oral dose (12 subjects) or three times a day for five days (4 subjects). A newly developed, high-pressure liquid chromatographic assay permitted selective, direct measurement of SSA in the presence of high concentrations of salicylic acid, one of its metabolites. Following a single dose, SSA was promptly absorbed (mean time to peak level 1.5 hour) and was eliminated from plasma with a mean half-life of 1.1 hour. Less than 1 per cent was excreted in the urine as unchanged SSA. SSA did not accumulate in the plasma during multiple dosing. Plasma levels of salicylic acid following single and multiple doses of SSA indicate that SSA is extensively hydrolyzed to salicylic acid in the body. The slightly lower levels of salicylic acid after SSA than after aspirin may reflect direct biotransformation of some of the SSA to an SSA conjugate, without hydrolysis to salicylic acid.