title: Pharmacokinetic behavior of argirein, derived from rhein, is characterized as slow release and prolonged T₁/₂ of rhein in rats.
abstract: OBJECTIVE
  Rhein is an effective ingredient from Rheum palmatum L., Polygonum cuspidatum Sielb.et Zucc., Polygonum multiflorum Thunb. and has anti-inflammatory activity, however, plasma levels are too high and T(1/2) is not long enough following oral medication. Therefore, a modification of the rhein moiety was encouraged to improve the pharmacokinetic behavior. Argirein was produced by connecting rhein with l-arginine through hydrogen bond, which releases both rhein and L-arginine while getting into the body. The present study was to verify if the pharmacokinetic profile of argirein by measuring the released rhein is improved against those of untreated rhein administered alone.
  
  
  METHODS
  A reversed-phase HPLC with a mobile phase of methanol mixed with acetate buffer was conducted. Rhein was monitored after arginine administration by i.g. and i.v. routes. Rhein alone was also administered and compared.
  
  
  RESULTS
  The C(max) and AUC(0-48) of the released rhein following argirein medication were less than those following rhein administered. The bioavailability of argirein was 18.5-20.8% against 22.77-25.22% of rhein. A delayed T(max), a reduced C(max) and AUC(0-t) and an increased T(1/2) were significant in the argirein group as compared with those in the rhein group.
  
  
  CONCLUSIONS
  The pharmacokinetic behavior of oral argirein presents a slow release property against those following oral rhein in rats. The released rhein following oral argirein is suitable in suppressing chronic inflammatory reactions attributed to prolonged T(1/2) and delayed T(max) due to its slow release pharmacokinetic characteristics.
authors.affiliation: Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Cong
authors.forename: Peng-Rong
authors.initials: PR
authors.lastname: Fu
authors.forename: De-Zai
authors.initials: DZ
authors.lastname: Dai
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yin
authors.initials: Y
authors.lastname: Dai
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000880:Anthraquinones / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D056148:Chromatography, Reverse-Phase / Q000592:standards; D003692:Delayed-Action Preparations; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
chemical_list: D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D011355:Prodrugs; C558481:argirhein; C020491:rhein