Pharmacokinetics of silybin following oral administration of silipide in patients with extrahepatic biliary obstruction.
The pharmacokinetics of silybin, the main active component of silymarin, following administration of a lipophilic silybin-phosphatidylcholine complex (silipide) was evaluated in fourteen patients with cholestasis secondary to biliary extrahepatic obstruction. Each patient received a single oral dose of silipide (120 mg, expressed as silybin equivalents). Blood samples for high performance liquid chromatography (HPLC) determination of free (unconjugated) and total (free+conjugated) silybin were collected at frequent intervals for up to 24 h after dosing. Absorption from the gastrointestinal tract occurred rapidly, peak concentrations of free drug being observed within 3 h in most patients. Thereafter, the decline in plasma free silybin levels was relatively rapid, 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 concentration. Total silybin levels reached a peak at about 3 to 4 h and persisted at relatively high values (> or = 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 under the curve for free silybin. These data suggest that extrahepatic biliary obstruction is associated with a reduced clearance of conjugated silybin, probably due to impaired excretion of the conjugate in bile.
Schandalik
R
R
Division of Surgery, Braunau Regional Hospital, Braunau-am-Inn, Austria.
Perucca
E
E
D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000494:pharmacology*; D001651:Cholestasis, Extrahepatic / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000494:pharmacology*; D012838:Silymarin / Q000493:pharmacokinetics* / Q000494:pharmacology*
D000975:Antioxidants; D010713:Phosphatidylcholines; D012838:Silymarin; C067772:IdB 1016