Studies On Biopharmaceutical Analysis And Preclinical Pharmacokinetics Of Polydatin

Polydatin (PD), 3, 4', 5-trihydroxystibene-3- β -D-mono-D-glucoside, is one of the active compounds in Chinese medicinal herb polygonum cuspidatum sieb. et zucc Huzhang Polygonaceae. Modern pharmacological studies have indicated that PD can be used to protect myocardium, inhibit the aggregation of platelets, and improve microcirculation. Besides, it also relief the harm to tissue or organ so as to protect the functions of liver cells, lower lipid and resist superoxidation of lipid, etc. Research works have been focused on the chemical structure, extraction, separation, and pharmacological effects of PD, but little information is available on the absorption, distribution, metabolism or excretion of PD. The preclinical pharmacokinetic data of PD is to be generated, which requires the development of an analytical method in different biomatrices.A reversed-phase high-performance liquid chromatographic (RP-HPLC) method has been developed for the determination of PD in beagle plasma, rat plasma, bile, urine, feces and tissue homogenates using 2,3,5,4'- tetrahydroxychrysophenine- β -D-glucoside as an internal standard. The sample pretreatment included deproteinization and solid-phase extraction for plasma samples and a liquid-liquid extraction for bile, urine, feces and tissue homogenates. Separation was obtained on a ₁8g reversed phase column with the mobile phase consisting of methanol and water (35:65,v/v). The flow rate was 1.0 ml/min and theeffluent was monitored at 290nm.The method described above has been successfully applied to determine PD concentrations in the various biological matrices with relatively high extraction efficiency and good separation selectivity. The accuracy, precision, sensitivity, specificity and linearity of this method well satisfied the requirements of pharmaceutical analysis in biological samples.The protein precipitation was used to treat the plasma samples of PD at different time in rats after i.v. 10, 20 and 30mg/kg of PD. The three plasma concentration-time curves obtained were similar. Concentration-time curves after i.v. 10, 20 and 30mg/kg of PD were fitting to a two-compartment open model. AUC were 807.54 g-min/ml, 953.73 g-min/ml and 1919.30 g-min/ml, respectively. The AUC values were linearly related to the dosages (r=0.920).The distribution of PD in rats was studied. The PD concentration were high in the liver, lung, kidney and intestine, moderate in the heart, spleen, ovaries, stomach, uterus and fat and low in the cerebrum, cerebellum, testicle and muscle. Data of the urine and bile excretion indicated that only a small percent of PD was excreted. The excretion of drug in urine amounted to only 1.51% of the dosage and in feces to 0.035% within 96h after dosing. The biliary excretion were only 1.11% of parent drug of the dosage within 24h after dosing.The solid-phase extraction was used to treat the plasma samples of PD from beagle dogs after i.v. administrations of three levels of dosage. The three plasma concentration-time curves obtained were similar.