PHARMACOKINETICS OF SILYBIN FOLLOWING ORAL-ADMINISTRATION OF SILIPIDEIN PATIENTS WITH EXTRAHEPATIC BILIARY OBSTRUCTION

The pharmacokinetics of silybin, the main active component of silymari n, following administration of a lipophilic silybin-phosphatidylcholin e complex (silipide) was evaluated in fourteen patients with cholestas is secondary to biliary extrahepatic obstruction. Each patient receive d a single oral dose of silipide (120 mg, expressed as silybin equival ents). Blood samples for high performance liquid chromatography (HPLC) determination of free (unconjugated) and total (free + conjugated) si lybin were collected at frequent intervals for up to 24 h after dosing . Absorption from the gastrointestinal tract occurred rapidly, peak co ncentrations of free drug being observed within 3h in most patients: T hereafter, the decline in plasma free silybin levels was relatively ra pid, and at 12 h the concentration of free drug had already approached the limit of quantitation (2 ng/ml). At all sampling times, the total (free + conjugated) concentration was much higher than the free conce ntration. Total silybin levels reached a peak at about 3 to 4h and per sisted at relatively high values (greater than or equal to 400 ng/ml) throughout the entire sampling period. On average, the area under the curve for total silybin was more than 40-fold greater than the area un der the curve for free silybin. These data suggest that extrahepatic b iliary obstruction is associated with a reduced clearance of conjugate d silybin, probably due to impaired excretion of the conjugate in bile .