RT Journal Article
SR Electronic
T1 Pharmacokinetics and Metabolism of Ligustilide, a Major Bioactive Component in Rhizoma Chuanxiong, in the Rat
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 400
OP 408
DO 10.1124/dmd.107.017707
VO 36
IS 2
A1 Yan, Ru
A1 Ko, Nga Ling
A1 Li, Song-Lin
A1 Tam, Yun Kau
A1 Lin, Ge
YR 2008
UL http://dmd.aspetjournals.org/content/36/2/400.abstract
AB Ligustilide is the most abundant bioactive ingredient in Rhizoma Chuanxiong, a Chinese medicinal herb commonly used for the treatment of cardiovascular ailments. The present study reported, for the first time, the pharmacokinetics of ligustilide, administered in its pure form and in an herbal extract, in rats. After i.v. administration of pure ligustilide, it was distributed extensively (Vd, 3.76 ± 1.23 l/kg) and eliminated rapidly (t1/2, 0.31 ± 0.12 h). The i.v. clearance (CL) of ligustilide after Chuanxiong extract administration was significantly higher than that dosed in its pure form [CL, 20.35 ± 3.05 versus 9.14 ± 1.27 l/h/kg, p < 0.01; area under the curve (AUC), 0.79 ± 0.10 versus 1.81 ± 0.24 mg · h/l, p < 0.01], suggesting significant interaction between ligustilide and components present in the extract. Dose-dependent pharmacokinetics was observed after i.p. administration, and a significantly higher dose-normalized AUC (1.77 ± 0.23 mg · h/l) at 52 mg/kg was obtained than that at 26 mg/kg (0.93 ± 0.07 mg · h/l, p < 0.05). Oral bioavailability of ligustilide was low (2.6%), which was partly because of extensive first-pass metabolism in the liver. Seven metabolites of ligustilide were identified, and three of them were unequivocally characterized as butylidenephthalide, senkyunolide I, and senkyunolide H. These three compounds also occurred naturally in the herb and were reported to be bioactive. The American Society for Pharmacology and Experimental Therapeutics