中文摘要：

目的研究海洋新骨架小分子南强菌素经单次静脉注射后在Wistar大鼠体内的药动学、组织分布及排泄特征。方法48只Wistar大鼠（雌雄各半）分为8组（每组雌雄各三只），3组分别尾静脉注射南强菌素10、20、30mg·kg^-1，液相色谱-串联质谱法（LC—MS／MS）测定其血药浓度，DAS2．0计算药动学参数；其余5组单次尾静脉给予南强菌素20mg·kg^-1，其中3组大鼠给药后0．5、2、3h麻醉处死、解剖测定南强菌素组织分布，1组给药后收集0—2h、〉2—4h、〉4～8h、〉8～24h的尿液粪便评价南强菌素的排泄过程，1组麻醉后插管收取0～2h、〉2～16h、〉16～24h胆汁评价胆汁排泄。结果大鼠分别静脉单次注射10、20、30mg·kg。南强菌素后，t1/2 2分别为（2．09±0．68）、（2．44±0．35）、（2．57±1．33）h，AUCo-8h分别为（3378±544）、（3492±460）、（4451±573）μg·h·L^-1；单次静脉给药20mg·kg^-1，0．5h后肾脏组织中的南强菌素含量最高（1736．8ng·^g-1），肺脏及脾脏次之；给药2h后，多数组织中已经检测不到或仅能检测到极少量南强菌素；原型药物经尿样和胆汁的排泄率分别为1．87％和0．91％，粪便的排泄率极低，低于总给药量的0．01％。结论单次给予南强菌素，各剂量组的AUC0-8h、ρmax和t1/2 2.用SPSS进行相关检验，无显著差异（P〉0．05），表明在置信度（单双侧）0．05水平上剂量与AUC0-8h、和t1/22均不相关；原型药物经粪便和尿样排泄率较低，1～24h内仅有1．87％从尿液中排出。

英文摘要：

AIM To evaluate the pharmacokinetics, distribution and excretion of deacetyl-mycoepoxydiene in rats. METHODS A total of 48 Wistar rats were divided into eight groups, a single intravenous dose of 10, 20, 30 mg·kg^-1 of deacetyl -mycoepoxydiene were given for the pharmacokinetics. A single intravenous dose of 20 mg· kg^-1 of deacetyl- mycoepoxydiene were given to a total of five groups, three groups of rats were sacrificed after anesthetized separately at 0.5, 2, 3 h for the tissues distribution, urine and faeces of one group were collected during 0 - 2 h, 〉 2 - 4 h, 〉 4 - 8 h, 〉 8 - 24 h for the excretion of urine and faeces, and bile of another group was collected during 0 - 2 h, 〉 2 - 16 h, 〉 16 - 24 h for biliary excretion. RESULTS The main pharmacokinetics parameters after intravenous administration at doses of 10, 20, 30 mg·kg^-1 were as follows： t1/22 （2.09 ± 0.68）, （2.44 ± 0.35）, （2.57 ± 1.33） h; AUC0-8h （3 378 ± 544）, （3 492 ± 460）, （4 451 ±573） μg·h·L^-1. The maximum concentration appeared in the kidney （1 736. 8 ng·g^-1） after a single dose of deacetyl-mycoepoxydiene 20 mg·kg^-1. The excretion rate of prototype drug through urine and bile were 1.87% and 0.91%. CONCLUSION After intravenous injection of deacetyl-mycoepoxydiene, AUC0-8h, ρmax and t1/2z demonstrate no linear relationship with the doses. The drug is widely distributed in kidney and 1.87% prototype is excreted through the urine within 1 - 24 h.