Pharmacokinetics of salicin after oral administration of a standardised willow bark extract

Objective: To evaluate the pharmacokinetics of salicin and its major metabolites in humans after oral administration of a chemically standardised willow bark extract. Methods: Willow bark extract corresponding to 240 mg salicin (1360 mg, 838 mu mol) was ingested by ten healthy volunteers in two equal doses at times 0 h and 3 h. Over a period of 24 h, urine and serum levels of salicylic acid and its metabolites, i.e. gentisic acid and salicyluric acid, were determined using reverse-phase high-performance liquid chromatography. Renal excretion rate, elimination half-life and total bioavailability of salicylates were calculated. Results: Salicylic acid was the major metabolite of salicin detected in the serum (86% of total salicylates), besides salicyluric acid (10%) and gentisic acid (4%). Peak levels were reached within less than 2 h after oral administration. Renal elimination occurred predominantly in the form of salicyluric acid. Peak serum levels of salicylic acid were on average 1.2 mg/l, and the observed area under the serum concentration-time curve (AUC) of salicylic acid was equivalent to that expected from an intake of 87 mg acetylsalicylic acid. Conclusion: Willow bark extract in the current therapeutic dose leads to much lower serum salicylate levels than observed after analgesic doses of synthetic salicylates. The formation of salicylic acid alone is therefore unlikely to explain analgesic or anti-rheumatic effects of willow bark.