Pharmacokinetics and metabolism of ligustilide, a major bioactive component in Rhizoma Chuanxiong, in the rat.
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 (V(d), 3.76 +/- 1.23 l/kg) and eliminated rapidly (t(1/2), 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 x 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 x h/l) at 52 mg/kg was obtained than that at 26 mg/kg (0.93 +/- 0.07 mg x 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.
Department of Pharmacology, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR.
Ru
R
Yan
Nga Ling
NL
Ko
Song-Lin
SL
Li
Yun Kau
YK
Tam
Ge
G
Lin
D015107:4-Butyrolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D004333:Drug Administration Routes; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005750:Gastric Juice / Q000737:chemistry; D007419:Intestinal Secretions / Q000737:chemistry; D030004:Ligusticum / Q000737:chemistry*; D008297:Male; D008861:Microsomes / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; C027820:ligustilide; D015107:4-Butyrolactone