Comparative pharmacokinetics of senkyunolide I in a rat model of migraine versus normal controls

Senkyunolide I is an active ingredient of Rhizoma Chuanxiong, a Chinese medicinal herb commonly used for the treatment of cardiovascular ailments. In the present paper, we describe the isolation and elucidation of senkyunolide I from the ethanol extract of Rhizoma Chuanxiong and its pharmacokinetic behavior after intravenous and oral administration to normal and migrainous rats. After intravenous administration, senkyunolide I was rapidly distributed (V ( z )/F 2.07 ± 0.43 L/kg) and eliminated from the plasma (CL( z ) 2.56 ± 0.29 L/h/kg and t (1/2z ) 0.56 ± 0.13 h). After administration orally to normal rats at two dosages (20 and 72 mg/kg), the pharmacokinetic parameters of senkyunolide I were as follows: T (max) 0.25 ± 0.06 and 0.38 ± 0.11 h, C (max) 5,236.3 ± 802.8 and 22,071.9 ± 3,456.1 mg/L, Area under the curve(AUC)((0-t)) 5,217.5 ± 1,029.5 and 21,480.2 ± 3,003.1 μg h/L, respectively. Its oral absolute bioavailability at the two dosages was 67.2 and 76.9%, respectively. Intriguingly, migraine caused some significant changes in its pharmacokinetic parameter. For example, when compared with its pharmacokinetic behavior in normal rats at the two dosages, on average, its clearance decreased by 68% and volume of distribution increased by 342% in migrainous rats, both of which contributed to its several-fold increase in t (1/2z) and AUC. C (max) and AUC of senkyunolide I increased almost proportionally with dose between 20 and 72 mg/kg and the pharmacokinetics fit linear kinetic feature. The pharmacokinetic parameters of senkyunolide I were significantly different in normal and migrainous rats, which should be taken into account during the design of a clinical dosage regimen for senkyunolide I.