280只大鼠随机分组,分别静脉滴注不同剂量的果糖1,6二磷酸镁(FDP-Mg),在给定时间点采血,酶法测定FDP血药浓度,原子吸收分光光度法测定Mg2+血药浓度,旨在研究FDP-Mg在大鼠体内的主要动力学特征.结果发现:大鼠尾静脉滴注FDP-Mg三种剂量后,Mg2+的血药浓度-时间曲线符合二室开放模型,其T1/2α为12.0～16.9min,T1/2β为103.59～118.46 min,分布容积Vd为1.61～1.78 L/kg,各剂量组间主要动力学参数CL、T1/2el、Vss AUC/X0经t检验差异无显著性(P＞0.05),显示非剂量依赖性特征.FDP的血浆消除半衰期T1/2el为8～10 min,MRT为19～22 min,CL为(0.011～0.031)L@kg-1@min-1.在125～500 mg/kg范围内,FDP呈线性消除,各剂量间主要动力学参数统计学差异无显著性.FDP和Mg2+的药代动力学特征差异较大,提示FDP-Mg经静脉注射进入生物体后,可解离为FDP、Mg2+两部分,二者分别按照各自的药代动力学特征从体内消除.

AIM　To compare the bioactivity and bioavailability of domestic and imported salcaltonin injections in Chinese healthy volunteers. METHOD　Using randomized cross design, to determine the concentrations of calcium and salcaltonin in serum of healthy volunteers after single dose of domestic and imported injections. RESULT　Two preparations reduced concentration of calcium in serum obviously and there was no difference of mean changes of calcium between the two kinds of injections (P>0.05). The main pharmacokinetic parameters are: Cmax: (2.31±0.16) μg*L-1 and (2.44±0.20) μg*L-1；Tmax: (48.75±12.99) min and (52.50±16.31) min；T1/2ke: (92.93±11.86) min and (97.61±11.23) min；Ke: (0.0079±0.0023) min-1 and (0.0084±0.0014) min-1；AUC(0～360 min): (297.70±44.45) μg*min*L-1 and (313.64±46.03) μg*min*L-1 respectively in domestic and imported salcaltonin injections. The relative bioavailability of domestic formulation is 97.6%±25.6%. CONCLUSION　The domestic and imported salcaltonin injections administered produce similar biological response and bioavailability and they are bioequivalent.

AIM To study the pharmacokinetic characters of dauricine(Dau) in rats after different administration ways. METHOD RP-HPLC method was used in the study. RESULT The results indicated that the plasma C-T curve conform to two- compartment open model after iv. The plasma concentra- tion of Dan in rats for ig Dan 150 mg.kg-1 is low, less than 1 mg.L-1 of peak concentration. The abso lute bioavailibility is about 16 .6 %. The plasma concentration-time profile shows a double-peak phe- nomenon The time taken to reach the peak is about 15 min after ig and the trough time is 3 h. The plasma concentration increased again in 4 h to form the second peak. The studies suppose a stomach-intestine recirculation of Dan is the major reason for doublepeak phenomenon. Dau has a wide distribution in rat body. It lies in all tissues and organs in both adminastration ways. The tissue Dan concentration are hundreds times higher than that in plasma concurrently. Faces is the main route whereby Dau are excreted from the rats after ig 150 mg. kg-1. The excreted percentage through feces is 26 .29 %, while through urine is 4.93%. The total amount is 31.22% after 48h of oral administration of Dau. The study of the mean percentage of the dose remaining in stomach, small intestine, large intestine and whole GI tract from each rat sacrificed at different times after oral administration of Dan suggest the stomach-intestine circle. CONCLUSION The bioavailibility of Dau is low. The plasma drug concentration versus time curve shows an innormal double-peak phenomenon. Dau can distribute abroadly to almost all kinds of the tissues in rats. The ban excretion routes are through feces and urine. The pilot study suggests that stomach-intestine circle be the main ran for the innormal double-peak phenomenon.

To establish the determination method of dauricine (Dau) concentration in rats’ blood and other biological samples, a reverse-phase HPLC method was adopted. Under the given condition, dauricine could be well separated. The retention time (tR) of Dau and its internal standard, daurisoline were 9.2 and 6.1 respectively. The detection limit was 10−2 mg/ml. The absolute recoveries of all kinds of samples were above 70 %, and the relative ones were over 85 %. A good liner relationship has been obtained over the entire range of 0.030 to 3.000 mg/L in blood samples and 0.050 to 5.000 mg/L in other tissue samples. The intraday and interday coefficients of variation were below 10 %. The results showed that the method can be used for detecting Dau in all kinds of biological samples.

To study the metabolism of dauricine in vivo and in vitro and identify the structure of its main metabolites, urine of rats after drug administration as the samples of dauricine metabolism in vivo was studied. Rat liver S9 fraction was prepared and the oxygenation metabolism system reconstituted to perform phase I reaction of dauricine in vitro. TLC, HPLC-DAD and MS were used to analyze and identify dauricine and its main phase I metabolites in the samples. The results showed that besides the untransformed dauricine, in the urine samples there was little product of X' which had the same features of TLC, HPLC-DAD and MS as those of N-desmethyl dauricine (N-ddau). Part of dauricine could be transformed to a main metabolite X after incubating with S9 fraction in appropriate conditions. The molecular ion peak of X was m/z 611. The full scan MS2 spectrum of m/z 611 peak from S9 sample were m/z 580, m/z 566, m/z 552, m/z 206, which were same as those of N-ddau. Liver is the major organ for dauricine metabolism and part of dauricine is biotransformed by liver. The major metabolite is considered to be N-ddau.

目的考察国产异丁司特缓释胶囊的人体相对生物利用度.方法12名男性健康受试者随机分为3组,分别口服单剂量日本产异丁司特缓释胶囊20mg、国产异丁司特缓释胶囊20mg、异丁司特原料药10mg,交叉自身对照.于服药后取静脉血,用HPLC法测定血清异丁司特浓度.结果三种制剂的Cmax分别为(54.9±9.7)、(60.7±9.1)、(62.2±11.5)μg·L-1,tmax分别为(3.8±0.8)、(3.9±0.8)、(1.75±0.34)h,t1/2(ke)为(11.5±1.4)、(12.1±1.0)、(3.5±0.5)h,AUC(0～t)为(618.1±57.7)、(588.2±66.6)、(233.0±46.4)μg·h·L-1.以日本杏林公司产品作为参比制剂,国产异丁司特缓释胶囊的人体相对生物利用度为(95.6±11.0)%.结论经双向单侧t检验,国产和进口缓释胶囊具有生物等效性,与原料药相比具有明显的缓释特性.

目的:研究国产鲑鱼降钙素注射液的生物等效性.方法:12名健康男性志愿者随机交叉肌肉注射单剂量国产鲑鱼降钙素注射液及进口鲑鱼降钙素注射液100 IU进行药代动力学和相对生物利用度研究.方法:酶免疫分析方法 (EIA) 测定血清中药物浓度.结果:肌肉注射鲑鱼降钙素后体内动力学过程符合一房室模型,国产及进口制剂的Cmax分别为2.31±0.16mg·L-1和2.44±0.20mg·L-1;Tmax分别为48.75±12.99 min和52.50±16.31 min;T1/2ke分别为 92.93±11.86 min和 97.61±11.23 min;Ke分别为 0.0079±0.0023 min-1和 0.0084±0.0014 min-1;CL(s)分别为0.018±0.004 L.min-1和0.017±0.003 L·min-1;V/F(c)分别为1.98±0.47L和1.97±0.29L;AUC(0～360)分别为297.70±44.45mg.min·L-1和 313.64±46.03mg.min·L-1.以进口产品为参比制剂,国产注射液的相对生物利用度为97.6±25.6%.两种注射剂的主要药代动力学参数经配对t检验无显著性差异(P>0.05),Cmax 、AUC(0～360)值对数转换后经方差分析、双向单侧t检验.结论:显示二者具有生物等效性.

Drug metabolism is an important part of pharmacokinetics. It has been paid more attention in worldwide studies and great progress has been achieved. As normal clinical therapeutic agents, antiarrhythmic drugs have their special metabolism characters. By knowledge of the site, routes and mechanisms of antiarrhythmic drugs' metabolism, as well as the factors affecting these processes, it is possible to increase the rationalization of drug using, to decrease the side effects and to provide direction for new drug development as well. Based on published papers, this article has reviewed the metabolism of antiarrhythmic drugs, emphasizing on the affecting factors including genetics, sex and drug interaction.

目的:研究不同产地蝙蝠葛几种主要生物碱在质与量上的区别.方法:采用有机溶剂提取生药,应用RP-HPLC方法对东北产和咸宁产蝙蝠葛根茎中几种主要脂溶性生物碱进行定性定量测定.结果:东北生药中含量最高的生物碱前3位依次是蝙蝠葛苏林碱、蝙蝠葛碱和guattegaumerine ;而咸宁药材则为蝙蝠葛碱、蝙蝠葛诺林碱及蝙蝠葛新诺林碱,不含蝙蝠葛苏林碱.结论:不同产地蝙蝠葛药材所含生物碱在质和量两方面均有显著差异.