Low oral bioavailability and pharmacokinetics of senkyunolide a, a major bioactive component in Rhizoma Chuanxiong, in the rat.
The pharmacokinetics of senkyunolide A, one of the major bioactive ingredients in the traditional Chinese medicinal herb Rhizoma Chuanxiong, which is commonly used for the treatment of cardiovascular diseases, was studied in rats. After intravenous (IV) administration, senkyunolide A was extensively distributed (Vd/F: 6.74 +/- 0.73 L/kg) and rapidly eliminated from the plasma (CL/F: 7.20 +/- 0.48 L/h per kilogram and t1/2: 0.65 +/- 0.06 hr). Hepatic metabolism was suggested as the major route of senkyunolide A elimination as indicated by the results of in vitro S9 fraction study. After intraperitoneal (IP) administration, senkyunolide A exhibited dose-independent pharmacokinetics. The absorption after IP administration was rapid (Tmax: 0.04 +/- 0.01 hours), and the bioavailability was 75%. After oral administration, senkyunolide A was also absorbed rapidly (Tmax: 0.21 +/- 0.08 hours); however, its oral bioavailability was low (approximately 8%). The contributing factors were determined to be instability in the gastrointestinal tract (accounting for 67% of the loss) and hepatic first-pass metabolism (accounting for another 25%). Pharmacokinetics of senkyunolide A were unaltered when Chuanxiong extract was administered, which suggests that components in the extract have insignificant effects on senkyunolide A pharmacokinetics.
Yan
Ru
R
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Lin
Ge
G
Ko
Nga Ling
NL
Tam
Yun Kau
YK
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001572:Benzofurans / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D005744:Gastric Acid / Q000737:chemistry; D006207:Half-Life; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D030004:Ligusticum; D008297:Male; D013058:Mass Spectrometry; D008657:Metabolic Clearance Rate; D008862:Microsomes, Liver / Q000378:metabolism; D008954:Models, Biological; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D027343:Rhizome / Q000737:chemistry*; D014018:Tissue Distribution
D001572:Benzofurans; D004365:Drugs, Chinese Herbal; C045855:3-N-butyl-4,5-dihydrophthalide; C101574:chuangxiong extract