Pharmacokinetic study of iodine-labeled silibinins in rat

The very low bioavailability of silibinin (silybin, SB), the main antioxida nt flavonolignan of silymarin front Silybum marianum L. (Asteraceae), requi res sensitive methods to study the modulation of silibinin bioavailability. To evaluate the potential for use of radiolabeled silibinin, two silibinin derivatives, separated by HPLC after iodination (I-125-SB1 and I-125-SB2) and their complexes I : I with phosphatidylcholine (I-125-SPC1 and I-125-SP C2) were administered concurrently with a single intragastric dose of 5.0 m g or 50 mg of unlabeled silibinin (alone or as a constituent of the complex ) per kg of body weight in a comparative study of bioavailability in the ra t. Pharmacokinetic parameters as well as organ uptake of I-125-SB1-derived radioactivity showed a dose-response pattern. The parameters of bioavailabi lity after I-125-SPC1 intake were not influenced by unlabeled silibinin (co mplexed with phosphatidylcholine), since maximal levels were achieved by th e lower dose of unlabeled compound. The superior bioavailability of I-125-S PC1 was obvious at the lower dose of unlabeled compound as elevated AUC and RA(max) (maximal percentage of administered radioactivity), and increased radioactivity in liver, kidney, spleen and heart. An absence of these chara cteristics with I-125-SB2 and I-125-SPC2 suggests the use of I-125-SB1 for studies of modulation of its bioavailability in vivo in rat. (C) 2001 Acade mic Press.