Studies On Preclinical Pharmacokinetics Of Vertilmicin And Trans-Resveratrol-3-O-Glucoside

Both vertilmicin and Trans-resveratrol-3-O-glucoside (PD-50) are two new candidate drugs in the stage of preclinical development. In this paper, Preclinical pharmacokinetics of vertilmicin and PD-50 was investigated to provide bases for their investigations and developments in the future.Vertilmicin (1-N-ethyl-verdamicin) is a new semisynthetic aminoglycoside derived from verdamicin whose 1-N position of 2-deoxystreptamine is ethylated. Based on the structure-activity relationship of chemical modification of aminoglycosides, new derivatives which 1-N position of 2-deoxy-streptamine is modified with an ethyl have lower toxicities and stronger actions to resistance-causing enzymes than those of intact structures. Experiment results had also shown that vertilmicin had strong biological activities against broad spectra of Gram-negative and positive bacteria.PD-50, a kind of stilbene glucosides isolated from different plants, exhibited various pharmacological activities, including preventing thrombosis from arterial endothelial damage, improving microcirculation and increasing survival rate of shocked rats, alleviating tissue-organ damage induced by ischemia-reperfusion, oxygen free radical and endotoxin, decreasing hyperlipemia, suppressing lipid peroxide, reducing the serum triglyceride, anti-lipid oxidation, anti-platelet aggregation and so on. These pharmacological actions of PD-50 enable it to become a new characteristic drug in treatment of thrombotic diseases and microcirculation in shock.1. Study on pharmacokinetics of vertilmicin in animalsVetilmicin lacks any useful chromophores or fluorophores structurally, so detection is usually achieved only after pre- or postcolumn derivatization. The high-performance liquid chromatographic determination of vertilmicin in biological fluids was developed using l-fluoro-2,4-dinitrobenzene (FDNB) as derivatization reagent. The pharmacokinetics of vertilmicin in rats and dogs were examined by the developed HPLC-UV method. After vertilmicin was intramuscularly administered to rats or dogs, absorption of vertilmicin was rapid and complete. The absolute bioavailabilities of vertilmicin in rats and dogs were 88.2% and 79.0%, respectively. The tissue distribution of vertilmicin was investigated at 0.25, 1.0 and 4.0 h postdose in rats. When 20 mg·kg^-1 of vertilmicin was administered intravenously to rats, vertilmicin was rapidly distributed into the most of tissues,...