title: Pharmacokinetic profiles of hydroxysafflor yellow A following intravenous administration of its pure preparations in healthy Chinese volunteers.
abstract: BACKGROUND
  Hydroxysafflor yellow A (HSYA), the major active marker compound isolated from Carthamus tinctorius L., has been demonstrated to possess various attractive pharmacological activities. However, there is a lack of information about the complete clinical pharmacokinetic profiles of HSYA following the administration of its pure preparations. The purpose of this study was to fully characterize the pharmacokinetic (PK) properties of HSYA in healthy Chinese volunteers following drip intravenous infusion of injectable powder of pure HSYA (IPPH), a new drug recently approved for the phase I clinical study by China Food and Drug Administration.
  
  
  METHODS
  36 healthy subjects of either sex were recruited in this single-center, and open-label, single doses (25, 50, and 75 mg) and multiple doses (50 mg, once daily, 7 consecutive days) study. Plasma samples were analyzed with a validated LC-MS/MS method. Various PK parameters were estimated from the plasma concentration versus time data using non-compartmental methods.
  
  
  RESULTS
  After single dose administration of IPPH, the values of AUC(0-t), AUC(0-∞) and C(max) for HSYA were statistically proportional over the dose range of 25-75 mg. After 7 repeated doses of 50 mg IPPH, both C(max) and AUC(0-∞) were significantly decreased, from 3207 to 2959 μg L(-1), and from 12,811 to 12,135 µg h L(-1) respectively, while t(1/2) was significantly prolonged from 3.912 to 4.414 h. The minimum plasma concentrations on day 5, 6 and 7 showed good stability with no significant difference. Both Cmax and AUC of HSYA in male volunteers were generally lower than that in females. IPPH was generally well tolerated in healthy volunteers by either single or multiple dosing.
  
  
  CONCLUSIONS
  HSYA displayed moderately linear PK properties over the doses ranging from 25 to 75 mg of IPPH. Repeated administration of IPPH once daily could not lead to the in-vivo drug accumulation, but significantly affect PK behavior of HSYA. Gender difference should be considered for dosage recommendation in the clinic.
authors.affiliation: Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing 210029, China.
authors.forename: Chang-Yin
authors.initials: CY
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing 210029, China.
authors.forename: Jun-Gang
authors.initials: JG
authors.lastname: Yin
authors.affiliation: Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing 210029, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing 210029, China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing 210029, China.
authors.forename: Mei-Juan
authors.initials: MJ
authors.lastname: Xu
authors.affiliation: Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing 210029, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing 210029, China.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Zou
authors.affiliation: Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing 210029, China. Electronic address: changyinli2008@126.com.
authors.forename: Wen-Zheng
authors.initials: WZ
authors.lastname: Ju
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D002599:Chalcone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D011809:Quinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D011809:Quinones; C085278:hydroxysafflor yellow A; D002599:Chalcone
keywords: Clinical pharmacokinetics; Gender difference; Hydroxysafflor yellow A; Pure preparations; safety assessment