前列安栓在大鼠体内的药代动力学研究

目的 :研究前列安栓在大鼠体内的吸收及分布 ,探讨中药复方药代动力学研究的方法 ,并为该药在临床上的合理使用提供依据。　方法 :雄性大鼠直肠给药 ,剂量为 5g生药 (2 0 0 μCi) /kg,于规定时间分批取血、前列腺、直肠及相关脏器测定放射性。　结果 :药后 5min即可从血液中测到放射性 ,血液药 时曲线符合开放型二室模型 ;药后 5min从靶器官 (前列腺 )中也测到放射性 ,药物放射性在前列腺中的富集浓度高于其它器官 (直肠、肝、肾除外 ) ,至 2 4h仍维持一定水平 ;除直肠外 ,药物放射性在肝、肾中的水平最高。　结论 :该药自直肠吸收迅速 ,并迅速到达靶器官 (前列腺 ) ,易于前列腺中富集 ,这对前列腺炎及前列腺增生的治疗有特殊意义 ;肝、肾可能是该药代谢和排泄的主要场所     

苯巴比妥对氯硝西泮药代动力学的影响及机理研究

 采用遗传性听源性癫痫模型(P<,77>-PMC)大鼠,从药代动力学角度研究了苯巴比妥(PB)对氯硝西泮(CZP)的影响,并对其机理进行了探讨.结果表明:PB使CZP各时间点的血药浓度都显著降低(P<0.01),使CZP的药代动力学参数发生相应的变化:半衰期(T<,1/2>)、曲线下面积(AUC)、峰浓度(Cmax)显著降低;清除率(CL)、表观分布容积(V/F)、清除速率常数(Ke)增高.另外PB对CZP的代谢有显著的促进作用是由于PB引起肝滑面内质网增多,使P<,450>酶显著增加所致.提示临床上PB与CZP合用时应结合临床,并参考血药浓度调整CZP的给药量.     

99Tcm-PnAO-硝基咪唑和99Tcm-HL91对乏氧心肌的实验研究

目的 探讨＾９９Ｔｃ＾ｍ－ＰｎＡＯ－硝基咪唑和＾９９Ｔｃ＾ｍ－ＨＬ９１２种乏氧心肌显像剂用于实验性心肌缺血、缺氧的作用。方法 进行小鼠体内分布与离体大鼠心脏模型研究,以９５％Ｏ２和５％ＣＯ２平衡的Ｋｒｅｂｓ－Ｈｅｎｓｅｌｅｉｔ缓冲液进行主动脉逆行灌注为对照组;以Ｎ２取代Ｏ２和ＣＯ２平衡的Ｋｒｅｂｓ－Ｈｅｎｓｅｌｅｉｔ缓冲液进行逆行灌注为乏氧组;以９５％Ｏ２和５％ＣＯ２平衡的Ｋｅｒｂｓ－Ｈｅｎｓｅｌ     

心肌灌注显像剂99Tcm-Q3的研制

目的研制新型心肌灌注显像剂９９ＴｃｍＮ,Ｎ′亚乙基二（乙酰丙酮亚胺）二［三（３甲氧基１丙基）膦］（简称Ｑ３）。方法合成显像剂的配体Ｎ,Ｎ′亚乙基—二（乙酰丙酮亚胺）和三（３甲氧基１丙基）膦后,用ＳｎＣｌ２·２Ｈ２Ｏ在强碱性条件下,还原９９ＴｃｍＯ－４标记Ｎ,Ｎ′亚乙基—二（乙酰丙酮亚胺）,再加入三（３甲氧基１丙基）膦反应１０ｍｉｎ,制得９９ＴｃｍＱ３。进行９９ＴｃｍＱ３小鼠体内分布和家兔显像实验,以及体外稳定性和急性毒性实验。结果９９ＴｃｍＱ３的心肌摄取快,摄取率高,注射后５ｍｉｎ时每克心肌组织的摄取约为注射剂量的２４６６％,滞留时间长,注射后４ｈ心肌清除不明显;血液、肺、肝脏清除均快。该显像剂无毒副作用,稳定性达６ｈ以上。结论９９ＴｃｍＱ３是提高心肌灌注显像质量的较理想的显像剂。     

Biodistribution of liposomal I-VIP in rat using gamma camera

Vasoactive intestinal peptide (VIP), a 28 amino-acid peptide was labeled with ¹³¹I and encapsulated into liposomes. ¹³¹I-VIP or liposomal ¹³¹I -VIP was administered intravenously into the rats. The distribution was studied by a gamma camera and established by counting the radioactivity in the removed organs. The elimination half-life for the liposomal ¹³¹I-VIP in both blood and lungs was significantly longer (5.29 and 9.28 min, respectively) than that obtained after the administration of ¹³¹I-VIP (0.62 and 3.18 min, respectively). Dynamic scans using a gamma camera after the administration of liposomal ¹³¹I-VIP showed a higher uptake of the liposomal form into the lungs compared with ¹³¹I-VIP. The lack of VIP in asthmatics has been shown in previous studies. However, the clinical investigations using VIP were disappointing most probably due to the rapid degradation of the peptide in the bronchial tract. This in fact is supported by our previous study, in which we demonstrated that VIP had a half-life of 0.45 min in blood. We conclude that the encapsulation of VIP in liposomes prolongs its elimination half-life in plasma and enhances its uptake in lungs. This observation may increase the clinical use of VIP in both diagnostic and therapy.     

Estimation of Topiramate in Subdural Cerebrospinal Fluid, Subcutaneous Extracellular Fluid, and Plasma: A Single Case Microdialysis Study

PURPOSE: To estimate topiramate (TPM) concentrations in subdural cerebrospinal fluid (CSF), subcutaneous extracellular fluid (ECF), and plasma and to study the correlation of TPM concentrations in these three different compartments. METHODS: In this single case study of a patient with drug-resistant partial epilepsy undergoing presurgical evaluation with subdural EEG monitoring, we used microdialysis to estimate concentrations of unbound TPM in CSF of the subdural space and ECF of abdominal subcutaneous tissue. Blood samples were drawn for estimation of TPM concentrations in plasma. RESULTS: The correlation between unbound TPM concentrations in subdural CSF and abdominal subcutaneous ECF was good. The mean ratio of ECF/CSF TPM concentration was 0.93 (SD+/-0.03) and the correlation coefficient was 0.98. The mean ratio of ECF/total plasma TPM was 0.75 (SD+/-0.06), and the correlation coefficient was 0.99. The mean ratio of CSF/total plasma TPM was 0.81 (SD+/-0.06), and the correlation coefficient was 0.97. CONCLUSIONS: Assuming a protein binding of TPM of approximately 13%. it is concluded that, based on nine microdialysis samples from a single subject, TPM levels in the CSF at the cortical surface are approximately the same as the unbound plasma levels. Additional patients should be studied to confirm the results.     

窗口版吸入麻醉药生理性隔室药代动力学电脑模型的设计和验证

目的 设计并验证窗口环境下运行的吸入麻醉药生理性隔室药动力力电脑模型,方法模型包含有麻醉环路和肺器官２个气相室和１２个组织室,以Ｒｉｇｇｓ原理描述药物在组织和器官中的处置。屏幕上设有麻醉机和呼吸机的仿真操作面板,同时具有１４个隔室计算结果的图形和数据输出。临床验证分七氟醚（ＳＥＶ）组和地氟醚（ＤＥＳ）组,每组３７例ＡＳＡⅠ～Ⅱ级病人,使用常规的麻醉方法,采集麻醉药呼气末浓度作为靶浓度,将其结果与模     

Radioimmunoassay for TA-0910, a new stable thyrotropin releasing hormone analogue and its metabolite, TA-0910 acid-type, in human plasma and urine

Radioimmunoassay (RIA) was investigated for the determination of TA-0910 and its main metabolite, TA-0910 acid-type, in human plasma and urine. TA-0910 is a new metabolically stable analogue of thyrotropin releasing hormone (TRH). Antiserum was raised in the rabbit against the 1-fluoro-2,4-dinitrophenyl derivative of TA-0910 or TA-0910 acid-type conjugated to keyhole limpet hemocyanin (KLH). The radioligand was prepared by iodination with ¹²⁵I of the histidine imidazole ring of TA-0910 or TA-0910 acid-type. Cross-reactivities of anti-TA-0910 or TA-0910 acid-type antiserum for TA-0910, its metabolite and related compounds were low. The calibration range was 0.02–5 ng ml⁻¹ using 100 μl human plasma or urine. Inter-day variations of TA-0910 and TA-0910 acid-type assay in plasma were 3.5–15.5 and 1.8–9.4%, respectively. The variations of the assay in urine were the same as those in plasma. The recovery of TA-0910 and TA-0910 acid-type spiked in plasma or urine samples was approximately 100%. Furthermore, this method was applied to the determination of TA-0910 and TA-0910 acid-type in human plasma and urine samples, for the evaluation of the pharmacokinetics of TA-0910 in humans. From the results it was demonstrated that he developed RIA was useful for the determination of TA-0910 and TA-0910 acid-type in human plasma and urine, and was applicable to pharmacokinetic studies in humans.     

治疗剂量丁胺卡那霉素药代动力学及耳毒性实验研究

目的　明确幼年动物对氨基糖甙类抗生素耳毒性有无更高敏感性。方法　用扫描电镜及光镜观察以等效人类治疗剂量下丁胺卡那霉素 (AMK)注射的 10只早产、31只新生、31只幼年及 31只成年豚鼠毛细胞 ,并用TDx法研究新生、幼年及成年组各 16只豚鼠药代动力学特征。结果　 (1)单剂给药证实各年龄组均为二室开放性模型 ,峰浓度及达峰时间差异无显著性 ,但新生组清除率较其他组明显降低 [分别为 (0 .0 0 44± 0 .0 0 11)、(0 .0 0 97± 0 .0 0 42 )和 (0 .0 0 88± 0 .0 0 14)L (min·kg) ,均P <0 .0 1],清除半衰期明显延长 ,[分别为 (71± 13)、(5 3± 11)和 (4 3± 8)min ,分别P <0 .0 5、P <0 .0 1],曲线下面积明显增大分别为 [(1146 2± 4317)、(8349± 1470 )和 (816 6± 32 13) ,均P <0 .0 1];幼年、成年组无差异。多次给药新生组血药浓度明显高于同时点幼年、成年组 ,新生及幼年组存在明显体内药物蓄积。 (2 )早产、新生组损伤出现早且严重 ,幼年组较成年组重 ;停药后毛细胞缺失数继续增多。结论　即使等效人类治疗剂量的AMK对幼年 (尤其早产和新生 )豚鼠耳蜗均有不同程度损害 ,并随用药时间延长而加重。幼年动物这种高敏感性与该药从体内排出慢、易蓄积有关     

高压液相色谱法测定莫雷西嗪在家兔的血药浓度及药代动力学

建立了反相高效液相色普法测定血浆中莫雷西嗪浓度。采用内标法。流动相为甲醇－水－０.0065mol.L~(-1)醋酸铵－冰乙酸（７５：２４：０.０１５,v/v/v/v）,二氯甲烷提取。血药浓度在５０～５０００ng.mL~(-1)范围内呈线性关系,相关系数0.9997,血浆最低检测浓度４ng.mL~(-1).。方法回收率９６～１０２％,日内、日间ＲＳＤ为０.7～3.2和２.3~4.0％。应用该法研究了兔静脉注射药动学,用二室模型拟合,消除相半衰期为6.35±2.23h。本法简便、回收率和灵敏度高、重复性好,分析周期短,适于临床药代动力学和药效学的研究。