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The comparative pharmacokinetics of Silipide (IdB 1016, a silybin-phosphatidylcholine complex) and silybin were investigated by measuring unconjugated and total plasma silybin levels as well as total biliary and urinary silybin excretion in rats following administration of a single oral dose (200 mg/kg as silybin). Mean peak levels of unconjugated and total silybin after IdB 1016 were 8.17 and 74.23 micrograms/ml respectively. Mean AUC (0-6 h) values were 9.78 and 232.15 h.micrograms.ml-1 indicating that about 94% of the plasma silybin is present in a conjugated form. After administration of silybin, plasma levels of both unconjugated and total compound were under the analytical detection limit. Cumulative biliary (0-24 h) and urinary (0-72 h) excretion values after administration of IdB 1016 accounted for 3.73% and 3.26% of the administered dose, respectively. After silybin administration, the biliary and urinary excretion accounted for only 0.001% and 0.032% of the dose respectively. Our results indicate a superior bioavailability of silybin administered orally as IdB 1016. This was due mainly to an impressive increase in gastrointestinal absorption.

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Silybin is the main active flavanolignan constituent in the extract of Silybam inarianwn. In order to increase its poor oral absorption, 1dB 1016, a complex with phosphatidylcholine, was synthesized (1, 2).The comparative pharmacokinetics of 1dB 1016 and silybin were investigated by measuring free and total plasma silybin levels, as well as total biliary and urinary excretion in rats following oral administration of a single dose (200 mg/kg as silybin). A specific and sensitive HPLC method (detection limit: 5 ng/ml) for the detection of silybin in biological fluids was developed.Peak levels of free and total silybin (mean values respectively 8 and 74 .tg/ml) were obtained 0.5 and 1 h after 1dB 1016 dosing. The respective AUG values (0-24 h) were 9 and 232 h .tg/ml, demonstrating that about 95 % of the plasma silybin is present in a conjugated from.After the administration of silybin, plasma levels were hardly detectable only during the first hour following the administration.Cumulative biliary excretion after 1dB 1016 administration (0-8 h) was 3.73% and urinary excretion (0-72 h) was 3.26% of the administered dose. As the prolonged urinary excretion indicates, the drug is readsorbed from the bile compartment through an enterohepatic recycle. The quantities excreted were respectively more than 2000 and 300 times higher than after administration of silybin alone.Our results indicate that 1dB 1016 is well absorbed in rats, probably due to its remarkable lipophilic character.Artemisia annua L. is used in traditional Chinese medicine and has been investigated as part of the search for novel antimalarial drugs. The major constituent responsible for the antimalarial activity of this plant is the sesquiterpene lactone artemisinin (QHS, qinghaosu) (1) and this constituent has been found to be particularly active against chloroquine-resistant Plasinodiwn falciparum in the treatment of cerebral malaria (2). We have reported that the antimalarial activity of artemisinin is markedly enhanced by the presence of such methoxylated flavones as casticin (3). Further investigation of R' R2 R' R R1 casticin H3c0 H3CO OCH, OH OCH, artemetin H3CO H3CO OCH, OCH3 OCH, ctirysotplenetin H,CO H3cO OCH, OCH3 OH chrysophenol-D H,CO H,cO OCH, OH OH circilineol H,cO H,CO H OCH, OH eupatorin H,CO H,CO OH OH OCH,the flavonoids of this plant yielded seventeen methoxylated flavonoids, three of which were new naturally occurring flavonoids. The major constituents were chrysosplenol-D (0.1% dw), chrysoplenetin (0.035% dw), eupatorin (0.019% dw) and cirsilineol (0.006% dw) with casticin (0.004% dw) as a minor constituent (4).Cell suspension cultures were developed using seed from plants high yielding in artemisinin. Cultures were maintained at 25°C under continuous illumination and sub-cultured every four weeks. Third generation cells were harvested, freeze-dried, and extracted successively with n-hexane, chloroform, and methanol. These extracts were assayed for antimalarial activity using an assay based on the incorporation of E'RJ-hypoxanthine int...

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