生物等效性和生物利用度杂志

抽象的

Preparation, Characterization and Pharmacokinetics in Vivo of Oxymatrine-Phospholipid Complex

Peng-Fei YUE, Hai-Long YUAN, Ming Yang and Wei-Feng ZHU

The aim of the present study was to prepare oxymatr ine– phospholipid complex to enhance oral bioavailabilit y of oxymatrine and to study its physicochemical propert ies and to compare the pharmacokinetic characteristics and bioavailability after oral administration of oxymat rine– phospholipid complex in rats. Using tetrahydrofuran as a reaction medium, oxymatrine and phospholipids were re- solved into the medium, after the organic solvent w as re- moved under vacuum condition, oxymatrine–phospholip id complex was formed. The new complex’s physicochemi- cal properties including differential scanning calo rimetry (DSC), X-ray diffraction (XRD), N-octanol/water Par ti- tion Coefficient were tested. The concentrations of oxymatrine after oral administration of oxymatrine– phos- pholipids complex and oxymatrine at different time in rats were determined by HPCE. The pharmacokinetic param- eters were computed by software program 3p87. The d ata showed that oxymatrine and phospholipids in the oxymatrine–phospholipid complex were combined by no n- covalent bond, not forming a new compound and the s olu- bility of oxymatrine –phospholipid complex in n-oct anol was effectively enhanced. The better hepatocytes pe rme- ability was obtained by the phospholipid complex. W e found that mean plasma concentration–time curve of oxymatrine after oral administration of oxymatrine– phos- pholipid complex and oxymatrine in rats was both in ac- cordance with open two-compartment model with first - order absorption. Pharmacokinetic parameters of oxymatrine ,physical mixture and the complex in ra ts were T max 1.71, 1.91and 2.17 h, C max 0.164,0.247 and 0.437 μ g·ml -1 , AUC 0– ∞ 2.87, 3.23 and 9.43 μ g·h·ml -1 , respectively. The bioavailability of oxymatrine in rats was incre ased remarkably after oral administration of oxymatrine– phos- pholipid complex comparing to oxymatrine and the ph ysi- cal mixture. This was mainly due to an impressive i m- provement of the lipophilic property of oxymatrine– phos- pholipid complex.