Pharmacokinetics of lithospermic acid B isolated from Salvia miltiorrhiza in rats.
The absorption and pharmacokinetics of an active component of Salvia miltiorrhiza, lithospermic acid B (LSB), was investigated after intravenous and oral administration of doses of 10 or 50 mg LSB/kg to rats. Concentrations of LSB were determined by a validated liquid chromatography/mass spectrometry (LC/MS/MS) assay method. After intravenous administration of 50 mg/kg, dose-normalized (10 mg/kg) area under the curve (AUC) (993 microg.min/ml) was significantly greater than that at 10 mg/kg (702 microg.min/ml). The slower clearance Cl-at 50 mg/kg could be due to saturable metabolism of LSB in rats, and this could be supported by significantly slower Cl(NR) and significantly greater 24-h urinary excretion of LSB at 50 mg/kg than at 10 mg/kg. Following oral administration of LSB, the extent of LSB recovered from the entire gastrointestinal tract at 24 h ranged from 41.2% to 23.3%. Although LSB was not detected (limit of quantitation 10 ng/ml) in plasma after oral dose of 10 mg/kg, the absolute oral bioavailability at 50 mg/kg was 5%. Since LSB was shown to have low permeability through the Caco-2 cell monolayers, the low bioavailability of LSB could be due to poor absorption and metabolism.
Kim
Hui Hyun
HH
College of Pharmacy and Medicinal Resources Research Institute, Wonkwang University, Iksan, Korea.
Kim
John
J
Ji
Hye Young
HY
Kim
Yoon Chul
YC
Sohn
Dong Hwan
DH
Lee
Byung Mu
BM
Lee
Hye Suk
HS
D000284:Administration, Oral; D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D053630:Depsides; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza
D001572:Benzofurans; D053630:Depsides; C076944:salvianolic acid B