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• W1007853786 abstract "Silibinin, the main active component of Silybum marianum is a hepatoprotective and antioxidant agent with antitumor effect, exhibiting very low aqueous solubility and oral bioavailability limiting its use in therapeutics. We characterized serum and tissue pharmacokinetics of SLB, calculated its absolute bioavailability and developed an open loop physiologically based pharmacokinetic (PBPK) model, after oral (per os, p.o) and intravenous (i.v.) administration in mice as water-soluble silibinin-hydroxypropyl-beta-cyclodextrin (SLB-HP-β-CD) lyophilized product. 60 C57Bl/6J mice were divided into groups of 5, each group representing one sampling time point. SLB-HP-β-CD lyophilized product was administered orally (50mg/kg) and i.v. (20mg/kg) after reconstitution with water for injection. Blood and tissue samples were collected at selected time points after animal sacrificed, properly treated and analyzed with HPLC-PDA for non-metabolized and total SLB. NONMEM pharmacokinetic analysis revealed a 2-compartment PK model to describe serum SLB pharmacokinetics, with zero order absorption after oral administration and was applied as forcing function to an open loop PBPK model incorporating heart, liver, kidneys and lungs. Tissue/plasma Kp values were estimated using i.v. data and can be used to predict tissue SLB distribution after oral administration. Absolute oral bioavailability of SLB from the lyophilized SLB-HP-β-CD product was 10 times higher than after administration of pure SLB." @default.
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• W1007853786 date "2015-09-01" @default.
• W1007853786 modified "2023-09-25" @default.
• W1007853786 title "Serum and tissue pharmacokinetics of silibinin after per os and i.v. administration to mice as a HP-β-CD lyophilized product" @default.
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• W1007853786 doi "https://doi.org/10.1016/j.ijpharm.2015.07.060" @default.
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