妊娠对大鼠吸入性全麻药血/气分配系数和组织/气分配系数的影响

目的 观察妊娠对大鼠吸人性全麻药血，气分配系数及组织，气分配系数的影响。方法 健康成年（3月龄）雌性妊娠（妊娠18—22d）和非妊娠SD大鼠各10只，分别为妊娠组和非妊娠组。腹腔注射戊巴比妥钠40mg／kg麻醉，经腹主动脉抽血用于测血，气分配系数，放血处死后，分别取心、肝、肾及脑组织并制成匀浆，采用注射器顶空二次平衡法经气相色谱仪测定七氟醚、异氟醚和氟烷的血，气分配系数及组织，气分配系数。结果与非妊娠组相比，妊娠组氟烷的血，气分配系数和脑，气分配系数降低（P〈0．05），七氟醚、异氟醚的血，气分配系数、肝，气分配系数、肾，气分配系数、心，气分配系数差异无统计学意义（P〉0．05）。结论 妊娠降低大鼠氟烷的血，气配系数和脑，气分配系数，但不影响七氟醚和异氟醚的血，气分配系数和组织，气分配系数。     

肾上腺素对氯普鲁卡因硬膜外阻滞患者药效学和药代动力学的影响

目的观察1:20万肾上腺素对3％盐酸氯普鲁卡因硬膜外阻滞患者药效学和药代动力学的影响。方法择期行下腹部手术患者20例,ASAⅠ或Ⅱ级,随机分为2组(n=10):盐酸氯普鲁卡因组(C组)和盐酸氯普鲁卡因加肾上腺素组(CE组)。分别用3％氯普鲁卡因6 mg·kg-1(C组)和含 1:20万肾上腺素3％氯普鲁卡因6 mg·kg-1(CE组)硬膜外阻滞,记录局麻药的起效时间、运动阻滞起效时间和给药后20min时运动阻滞程度;分别在给药前及给药后3、6、9、11、13、15、17、20、30、45、60、 90min采取桡动脉血1．5ml,高效液相色谱法检测血浆氯普鲁卡因浓度,经计算机软件拟合血药浓度 -时间曲线,并计算各项药代动力学参数。结果两组局麻药的起效时间、运动阻滞起效时间和运动阻滞程度差异无统计学意义。C、CE组血药浓度峰值(Cmax)分别为0．49±0．47、(0．32±0．22)mg· L-1,达峰值时间(Tmax)分别为8±3、(9±4)min;血药浓度曲线下面积(AUC)分别为10±6、(7±4)μg· min·ml-1;清除速率常数(K)分别为0．32±0．21、(0．36±0．32)min-1;两组间Cmax、Tmax、AUC及K比较差异无统计学意义(P>0．05)。结论 1:20万肾上腺素对3％盐酸氯普鲁卡因硬膜外阻滞的药代动力学和药效学没有影响。     

高效液相色谱法测定人血浆中阿莫西林浓度及药代动力学

高效液相色谱法测定人血浆中阿莫西林浓度及药代动力学谭力周继红罗楠袁倚盛（南京军区南京总医院中心仪器分析科，南京２１０００１）阿莫西林（ａｍｏｘｉｃｉｌｉｎ）为β内酰胺类抗生素，其抗菌谱广，口服受食物影响小，对大多数病人耐受性良好，因而在临床上得以广泛...     

老年充血性心衰患者地高辛药代动力学研究

目的 :探讨老年心衰患者地高辛维持量的合理应用。　 方法 :用荧光偏振免疫分析法测定了 14例老年心衰患者血清地高辛浓度 ,并计算出药代动力学参数。　 结果 :14例老年心衰患者地高辛 t1/ 2 β,β和 Vd分别为 72 .769± 2 9.768h、0 .0 11± 0 .0 0 6h-1和 3.190± 3.30 0 L/ kg,与非老年心衰患者 ( t1/ 2 β 36.1± 2 .0 h,56.3± 12 h,β 0 .0 19± 0 .0 0 1h-1,Vd 7.37± 1.65L / kg)相比差异显著。　 结论 :老年心衰患者地高辛维持量以小量分次给药为宜 ,且更应注意个体化     

国产头孢三嗪在急性感染病人中的药代动力学

静脉滴注国产头孢三嗪0.5～1克,治疗8例急性感染病人的药代动力学。静注后半小时用HPLC测得的平均血药浓度为100.75μg/ml,24小时的血药浓度为11.4μg/ml,国产头孢三嗪的药代动力学特点与国外同类产品基本一致。半衰期长,清除半衰期为8.8小时,可在血液和感染部位中保持较长时间的杀菌和抑菌浓度,总表观分布容积为13.0L/kg,表明药物在组织中的浓度高。本品用量小,每日1克1～2次即可达到疗效。5例慢性胆囊炎伴胆石症患者静滴头孢三嗪1克后,2小时胆汁的平均药物浓度为1022.8μg/ml,可作为治疗胆道感染的有效药物。     

Buffering the stomach content enhances the absorption of diflunisal in man

Diflunisal, a lipophilic salicylate, is absorbed more slowly in healthy volunteers than aspirin. In this paper we report on attempts to influence diflunisal absorption by buffering the gastric milieu. Sodium bicarbonate given together and 30 min after diflunisal tablets significantly (p less than 0.05) shortened the time to reach peak plasma concentration (tmax greater than 15 per cent), raised maximum plasma concentration slightly (Cmax 6 per cent) and increased the area under the plasma concentration-time curve (AUC greater than 8 per cent). Other pharmacokinetic parameters, including terminal half-life and renal elimination of the compound, were not considerably influenced. These findings indicate that the absorption of diflunisal was enhanced by increased gastric pH, presumably a result of an increased solubility of diflunisal in the stomach together with faster transport into the small intestine. In one volunteer, after intravenous administration diflunisal plasma concentrations declined in a triphasic manner with a terminal half-life of 12.8 h. The volume of distribution was approximately 10 per cent of body weight. Based on the ratio of AUC after equivalent i.v. and oral diflunisal doses, the absolute bioavailability was 89.5 per cent.     

肝靶向抗病毒药Lac-PLL-ACV的制备及其趋肝性研究

目的：减少抗病毒药阿昔洛韦（Acyclovir,ACV）在治疗乙型肝炎中的肝外毒副作用，获得肝靶向ACV偶联物。方法：多聚赖氨酸（Poly-L-lysine,PLL)在氰硼酸钠的催化作用下与乳糖反应生成乳糖化多聚赖氨酸，乳糖化多聚赖氨酸与咪唑化阿昔洛韦在37℃pH9.5的条件下反应合成偶联物乳糖化多聚赖氨酸－阿昔洛韦（Lactosaminated poly-L-lysine-acyclovir,Lac-PLL-ACV）。偶联物经尾静脉注射进入小鼠体内后，收集小鼠血浆及肝脏样品，用高效液相色谱法测定药物浓度，研究遇联物的体内分布和药代动力学。结果：HPLC检测证实Lac-PLL-ACV在血浆中十分稳定，不易解离出ACV。偶联物的肝最大摄取率约为60％，是ACV组的10倍以上，偶联物肝中的T1／2，AUC，CL分别为ACV的4．2倍，56．6倍和1／57，具有明显的肝靶向性。结论：乳糖化多聚赖氨酸作为肝去唾液酸糖蛋白受体（Asialoglycoprotein receptor,ASGPR)介导的一种药物载体，能使抗病毒药ACV获得较满意的肝靶向性。     

LC—MS法测定人血浆中克林霉素浓度及药代动力学研究

目的 :建立人血浆中克林霉素浓度的高效液相色谱 -质谱法 ,测定志愿者口服盐酸克林霉素胶囊后的血药浓度 ,并对供试制剂和参比制剂的生物等效性进行评价。方法 :血浆中加入内标西沙必利后碱化 ,以乙酸乙酯提取 ,进行高效液相色谱 -质谱法检测。色谱柱为 Kromasil ODS1 5 0× 4 .6 mm,5 μm,流动相为甲醇 -1 %冰醋酸 ( 5 7∶ 4 3) ,流速 0 .8ml/min,质谱检测采用选择性离子检测方法。 2 0名健康志愿者随机分成两组 ,分别服用供试胶囊和参比胶囊 ,临床实验方案采用双交叉实验设计法。结果 :克林霉素的线性范围为 0 .0 0 5～ 1 5 μg/ml,最低检测浓度为 1 ng/ml,本测定方法的提取回收率在 1 0 0 .5 %～ 1 0 5 .2 % ,用本法测定了 2 0名志愿者随机交叉口服单剂量 6 0 0 mg后血浆中药物的浓度经时变化过程 ,并对其药动学参数进行估算。测得的 2种胶囊的主要药代动力学参数无显著性差异。结论 :该法简便 ,准确 ,灵敏度高     

Physiological pharmacokinetics and pharmacodynamics of (+/-)-verapamil in female rats

Tissue distribution and pharmacodynamics of verapamil were evaluated during steady state intravenous (i.v.) infusion and after single dose intraperitoneal (i.p.) drug administration to female Sprague-Dawley rats. In one group of rats, verapamil was infused to a steady state concentration at which time animals were killed. Verapamil-induced decreases in mean arterial pressure (MAP) were monitored during infusion and correlated with concomitantly obtained plasma verapamil concentrations. Tissue (lung, liver, renal medulla, renal cortex, cardiac muscle, skeletal muscle, perirenal fat, brain stem, cerebral cortex, and cerebellum) and plasma samples were obtained immediately after animals were killed and verapamil and norverapamil concentrations determined. Another group of rats, after receiving i.p. verapamil, were killed at 1, 3, 5, 19, and 24 h. Elimination from each tissue evaluated was described by a first order process. Elimination half-life of verapamil was similar among plasma and tissues evaluated (1.5 to 2.2 h). The per cent verapamil not bound to plasma proteins was concentration-independent and similar between rats receiving i.p. (mean +/- S.D.) (2.28 +/- 0.72 per cent) and i.v. (2.08 +/- 0.03 per cent) verapamil. MAP and verapamil concentration in plasma (r = 0.75; p less than 0.01) and cardiac muscle (r = -0.82; p less than 0.01) were inversely correlated in a highly significant fashion during both i.v. and i.p. drug administrations. The tissue-to-plasma distribution ratio for verapamil and norverapamil was similar among animals receiving i.p. verapamil at all points of sampling, suggesting distribution equilibrium had been achieved. After steady state i.v. infusion, both verapamil and norverapamil tissue: plasma concentration ratios were greater than after i.p. administration. Higher tissue: plasma verapamil concentration ratios after i.v. administration than after i.p. administration suggest either only a pseudoequilibrium is attained after i.p. administration or that determinants of tissue distribution of racemic verapamil differ with different routes of drug administration. In these studies, MAP provided a reasonable pharmacodynamic marker for verapamil tissue and plasma concentrations.