Pharmacokinetics and excretion of hydroxysafflor yellow A, a potent neuroprotective agent from safflower, in rats and dogs.
Studies were conducted to characterize the pharmacokinetics and excretion of hydroxysafflor yellow A (HSYA) in rats and dogs after administration by intravenous injection or infusion. Plasma, urine, feces and bile concentrations of HSYA were measured using five validated mild HPLC methods. Linear pharmacokinetics of HSYA after the intravenous administrations were found at doses ranging from 3 to 24 mg/kg in rats and from 6 to 24 mg/kg in dogs. At a dose of 3 mg/kg, HSYA in urine, feces and bile was determined. For 48 h after dosing, the amount of urinary excretion accounted for 52.6 +/- 17.9 % (range: 31.1 - 78.7%, n = 6) of the dose, and the amount of fecal amount accounted for 8.4 +/- 5.3% (range 1.7 - 16.4%, n = 6) of the dose. Biliary excretion amount accounted for 1.4 +/- 1.0% (range 0.4-2.9%; n = 6) of the dose for 24 h after dosing. Percent plasma protein binding of HSYA ranged from 48.0 to 54.6% at 72 h. In summary, five mild HPLC methods for the determinations of HSYA in rat plasma, urine, feces, bile and dog plasma have been developed and successfully applied to preclinical pharmacokinetics and excretion of HSYA in rats and dogs. The results of excretion studies indicated that HSYA was rapidly excreted as unchanged drug in the urine. In view of previous pharmacological work, the concentration-dependent neuroprotective effect of HSYA in rats was defined.
Research Center for Drug Metabolism, College of Life Science, Jilin University, Changchun, People's Republic of China.
Dafeng
D
Chu
Wanhui
W
Liu
Zhuo
Z
Huang
Shengsheng
S
Liu
Xueqi
X
Fu
Ke
K
Liu
D000818:Animals; D019540:Area Under Curve; D001646:Bile / Q000378:metabolism; D031187:Carthamus tinctorius; D002599:Chalcone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D004285:Dogs; D005243:Feces / Q000737:chemistry; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D008517:Phytotherapy; D010860:Pigments, Biological / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D010936:Plant Extracts / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D011485:Protein Binding / Q000187:drug effects; D011809:Quinones / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D010860:Pigments, Biological; D010936:Plant Extracts; D011809:Quinones; C085278:hydroxysafflor yellow A; D002599:Chalcone