Pharmacokinetic studies with silymarin in human serum and bile.

Six subjects were given orally 560 mg of silymarin (silibinin 240 mg = 8 Legalon 70 dragees). The serum concentration curves and urinary excretion of silibinin, the principal constituent of silymarin, were measured. The maximum serum concentrations were low, ranging from 0.18 to 0.62 microgram/ml. The same was true of renal excretion, which amounted to only 1-2% of the silibinin dose over 24 hours. However, after giving 140 mg of silymarin (silibinin: 60 mg) to patients who had undergone cholecystectomy, bile collected from the T-tube drains was found to contain maximum silibinin concentrations of between 11 and 47 micrograms/ml. Though the dose was four times lower than in the previous experiments, these concentrations were approximately 100 times higher than in the serum. Because complete collection of bile from these patients was impossible and because it was not possible to collect individual samples in the time interval from 12-24 h, the conventional pharmacokinetic parameters required for bioavailability studies could not be calculated. However, computation of the value for AUC0-24 and for "mean time" (MT) provided data which enabled bioavailability comparisons to be made. A study in which the absorption of Legalon 35 and Legalon 70 dragees was compared provides an example for such bioavailability investigations in the bile.