新抗病毒抗生素17997的药物代谢与动力学研究

Pharmacokinetics of 17997 in experimental animals were invetigeted. The plasma concentrations in rabbits and in dogs after iv injection at different time have been measured and better fitted the two-compartment model with first kinetics process. The main pharmacokinetic parameters of the three doses of 4, 2 and 1 mg·kg-1 in rabbits were followed: C0 were 4.15, 2.14 and 1.58μg?mL-1; AUC were 97.22, 40.54 and 21.00 min?μg?mL-1, T1/2β were 46.62, 48.20 and 42.16 min, respectively. The main pharmacokinetic parameters of the three doses of 1, 0.5 and 0.25 mg·kg-1 in dogs were followed: C0 were 0.80, 0.52 and 0.30μg?mL-1; AUC were 22.97, 12.30 and 7.58 min?μg?mL-1; T1/2β were 114.72, 115.25 and 117.74 min, respectively. The tissue concentration of 17997 in rats after a intravenous dose of 4 mg·kg-1 was high in lung, duodenum, liver, heart, kidney, spleen, thymus, serum and lymphnode at 15min, which were 16.55μg/g, 7.34μg/g, 6.51μg/g, 4.18μg/g , 3.31μg/g, 3.12μg/g, 1.83μg/g, 1.40μg/ml and 0.74μg/g，respectively. The ratio of tissue to plasma concentration in lung, liver, heart, kidney and spleen were 11.8, 4.7, 3.0, 2.4 and 2.2, respectively. The accumulative excretions of 17997 in 24h in rat bile at doses of 4 and 1 mg·kg-1 were (55.4±9.4)% and (58.8±11.8)%, respctively. The accumulative excretions of 17997 in 24h in rabbit urine were less 1.5%. The binding rate of an 17997 to rabbit plasma protein was 87.21%. The in vivo an in vitro metabolisms of 17997 showed that no metabolites were observed. Our study will provide basis for clinic and structural modification, and provide a new idea for antiviral drugs.

17997系从科学基金重大项目中获得的、产自云南土壤放线菌的代谢物，对疱疹病毒及人免呷毕莶《镜忍迥谕饬菩б讶范ǎ呛塑绽唷⒎悄孀济敢种萍痢Ｓτ猛凰厣锉昙呛虷PLC/MS/MS等分离分析方法，研究17997药物代谢与动力学，弄清其体内外动态变化规律及特点，将为临床研究和进一步结构修饰提供依据，为抗病毒创新药物研究提供新思路。