Pharmacokinetic behavior of argirein, derived from rhein, is characterized as slow release and prolonged T1/2 of rhein in rats

AimRhein 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 T1/2 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.MethodsA 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.ResultsThe Cmax and AUC0–48 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 Tmax, a reduced Cmax and AUC0–t and an increased T1/2 were significant in the argirein group as compared with those in the rhein group.ConclusionThe 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 T1/2 and delayed Tmax due to its slow release pharmacokinetic characteristics.