兔静脉滴注莫昔沙星眼内组织分布及其药动学研究

目的:探讨兔静脉滴注莫昔沙星后的眼内组织分布及药动学参数。方法:30只兔,随机分为10组(各组3只6眼),静脉滴注给予莫昔沙星,给药后0.125、0.25、0.5、1.0、2.0、3.0、4.0、6.0、8.0、12.0h取泪液、角膜、房水、虹膜-睫状体、玻璃体和晶体组织,高效液相色谱法测定各组织中药物浓度,3p97计算药动学参数。结果:给药后泪液、角膜、房水、虹膜-睫状体、玻璃体和晶体组织中Cmax分别为(31.90±11.22)、(3.27±0.48)、(3.71±0.54)、(2.93±0.53)、(3.62±0.24)、(1.21±0.16)μg.g-1/μg.mL-1;t1/2β分别为(2.57±0.90)、(3.09±0.42)、(2.30±0.49)、(1.89±0.80)、(3.30±0.52)、(3.30±0.43)h;AUC0→t分别为(135.18±44.34)、(12.06±0.96)、(7.51±1.03)、(8.51±2.19)、(12.99±2.42)、(6.47±0.52)μg.h.g-1/μg.h.mL-1。结论:兔静脉滴注莫昔沙星后在眼内各组织中有较高的药物浓度,且维持时间较长。     

兔单剂量灌服莫昔沙星眼内组织分布及其药动学研究

目的:探讨兔单剂量灌服莫昔沙星后的眼内组织分布及药动学参数。方法:30只兔,随机分为10组(各组3只6眼),灌服莫昔沙星24mg·kg-1后0.25、0.5、1.0、1.5、2.0、3.0、4.0、6.0、8.0、12.0h取泪液、角膜、房水、虹膜-睫状体、玻璃体和晶体组织,高效液相色谱法测定各组织中药物浓度,3p97计算药动学参数。结果:给药后泪液、角膜、房水、虹膜-睫状体、玻璃体和晶体组织中Cmax分别为(84.32±54.83)、(20.03±3.48)、(8.98±1.73)、(19.59±2.59)、(7.12±0.72)、(2.77±0.18)μg.g-1/μg.mL-1;t1/2β分别为(4.03±1.16)、(4.32±0.77)、(3.92±0.41)、(4.80±0.57)、(7.02±1.15)、(7.51±0.55)h;AUC0～t分别为(306.87±69.76)、(43.74±3.98)、(18.18±0.29)、(49.25±2.90)、(18.82±0.34)、(12.96±0.67)μg.h.g-1/μg.h.mL-1。结论:兔单剂量灌服莫昔沙星后在眼内各组织中有较高的药物浓度,且维持时间较长。     

环丙沙星滴眼液滴眼的眼内组织分布及其药代动力学研究

对环丙沙星滴眼液滴眼后家兔眼各组织中药物浓度用高效液相色谱法进行测定。结果表明,环丙沙星滴眼液滴眼后迅速进入眼组织,其中角膜浓度最高,其次为虹膜—睫状体、房水、晶体和玻璃体。各组织中的药物消除半衰期(T_(1/2β))分别为泪液0.81h、晶体0.61h、玻璃体1.40h;峰浓度值(Cmax)分别为角膜19.43μg/g、房水1.58μg/g、虹膜—睫状体16.68μg/g、晶状体1.42μg/g、玻璃体0.96μg/ml。实验结果提示环丙沙星滴眼液滴眼后能在眼内达到较高的抗菌浓度。     

莫昔沙星滴眼剂兔眼内组织分布及其药动学研究

目的:探讨莫昔沙星滴眼剂兔眼内组织分布及药动学。方法:将27只兔均分为9组,双眼滴0.2%莫昔沙星滴眼液100μL,分别于给药后0.125、0.25、0.5、1.0、2.0、3.0、4.0、6.0、8.0 h取样,采用高效液相色谱法测定泪液、角膜、房水、虹膜-睫状体、晶体和玻璃体组织中药物浓度,以3p97程序计算药动学参数。结果:泪液、角膜、房水、虹膜睫状体、晶体和玻璃体组织中最高药物浓度分别为(76.90±28.11)、(7.68±4.18)、(1.56±0.46)、(1.00±0.42)、(0.065±0.020)、(0.030±0.014)μg·g~(-1)或μg·mL~(-1);各组织中t_(1/2β)分别为(3.59±1.81)、(4.83±3.41)、(1.80±0.56)、(4.57±3.68)、(2.36±0.65)、(2.98±2.52)h; AUC_(0(?))分别为(75.95±17.57)、(10.68±1.57)、(2.30±0.44)、(2.86±0.42)、(0.74±0.38)、(0.086±0.042)μg·h·g(-1)或μg·h·mL~(-1)。结论:莫昔沙星易于渗透到眼内各组织,且有较高浓度。     

环丙沙星滴眼液滴眼的眼内组织分布及其药代动力学研究

对环丙沙星滴眼液滴眼后家兔眼各组织中药物浓度用高效液相色谱法进行测定。结果表明，环丙沙星滴眼液滴眼后迅速进入眼组织，其中角膜浓度最高，其次为虹膜—睫状体、房水、晶体和玻璃体。各组织中的药物消除半衰期（T1/2β）分别为泪液0.81h、晶体0.61h、玻璃体1.40h；峰浓度值（Cmax）分别为角膜19.43μg/g、房水1.58μg/g、虹膜—睫状体16.68μg/g、晶状体1.42μg/g、玻璃体0.96μg/ml。实验结果提示环丙沙星滴眼液滴眼后能在眼内达到较高的抗菌浓度。     

家兔静脉注射左氧氟沙星后的眼内组织分布及其药动学研究

目的:研究家兔静脉注射左氧氟沙星后的眼内组织分布及药动学。方法:27只家兔单剂量静脉注射左氧氟沙星(24mg/kg)后0.125、0.5、1.0、2.0、3.0、4.0、6.0、8.0、12.0h处死并取眼球各组织制备成匀浆,以高效液相色谱法测定眼内各组织中的药物浓度,3p97软件计算药动学参数。结果:给药后房水、角膜、虹膜-睫状体、玻璃体和晶体组织中药物cmax分别为(4.93±0.83)μg/ml,(6.12±0.71)、(6.02±0.55)、(1.98±0.28)、(1.38±0.12)μg/g;tmax分别为(0.50±0.00)、(0.83±0.26)、(0.71±0.71)、(0.52±0.28)、(0.67±0.26)h;t1/2β分别为(2.53±0.65)、(3.20±0.32)、(3.34±0.46)、(2.74±0.78),(2.49±0.45)h;AUC0-12h分别为(11.46±1.42)μg·h/ml,(28.01±1.59)、(26.01±2.34)、(8.16±0.85)、(5.23±0.89)μg·h/g。除房水为二室模型外,其余均呈一室模型分布。结论:家兔单剂量静脉注射左氧氟沙星后在眼内各组织中分布浓度较高,达峰时间较快,但保留时间相对较短。     

乳酸左氧氟沙星滴眼液在兔眼中的药动学

目的：测定乳酸左氧氟沙星（levofloxacin,LVFX)单次滴眼后不同时间兔眼组织的浓度,计算其药动学参数,研究药动学特点,方法：取32只大白兔分为8组,各组于用药后0．125,0．25,0．50,0．75,1．0,2．0,3．0,4．0h取眼组织,所有检测均采用高效液相色谱法。结果：药物在眼组织Tmax分别为：房水0．940h,虹膜－睫状体0．533h,角膜0．686h,玻璃体0．602h,晶状体0．609h,Cmax分别为：房水0．592μg.ml^-1,虹膜一胰状体1．007μg．g^-1,角膜5．340μg.g^-1,玻璃体0．112μg.ml^-1,晶状体0．124μg.g^-1,T1／2（Kα）：房水0．479h,虹膜一睫状体0．183h,角膜0．192h,玻璃体0．258h,晶状体0．175h,T1/2(Ke)：房水0．919h,虹膜一胰状体0．922h,角膜1．741h,玻璃体0．737h,晶状体1．462h,经用3P97药动学程序拟合符合一室开放模型。结论：单次滴眼在兔眼各组织中LVFX峰浓度均高于大多数致病菌的MIC90,LVEX滴眼液可用于眼内感染的临床治疗和预防。     

静注左氧氟沙星在兔血与眼组织中的药动学

目的:研究家兔静脉注射左旋氧氟沙星(LVFX)后在血液与眼组织中的分布以及药代动力学参数.方法:用高效液相色谱法测定给药后不同时点家兔血液和眼内各组织的药物浓度.结果:角膜、房水、虹膜-睫状体、晶状体和玻璃体内峰浓度值(Cmax)分别为(10.7±0.8)、(3.0±0.2)、(18.4±1.4)、(2.4±0.2)和(1.6±0.2)μg·g-1或mg·L-1.其血液和各组织中消除半衰期(T1/2β)分别为(3.2±0.4)、(9.2±2.9)、(9.1±1.9)、(7.7±1.1)、(6.2±1.3)和(5.5±1.0)h.结论:LVFX静脉注射后具有良好的眼内通透性,在眼组织中存留时间长,有助于维持眼内组织的有效血药浓度.     

家兔灌服左氧氟沙星后眼内组织分布及其药动学研究

目的:研究家兔单剂量灌服左氧氟沙星后的眼内组织分布及药动学。方法:27只家兔单剂量灌服左氧氟沙星(24mg·kg-1)后0.125、0.5、1.0、2.0、3.0、4.0、6.0、8.0、12h处死并取眼球各组织制备成匀浆,高效液相色谱法测定眼内各组织中药物浓度,3p97软件计算药动学参数。结果:给药后房水、角膜、虹膜-睫状体、玻璃体和晶体组织中cmax分别为(1.59±0.38)、(8.51±2.72)、(10.58±1.17)、(1.17±0.19)、(1.28±0.39)μg·g-1/μg·mL-1;tmax分别为(0.67±0.24)、(1.00±0.55)、(1.83±0.41)、(0.60±0.34)、(0.75±0.27)h;t1/2β分别为(2.68±0.70)、(3.87±1.24)、(5.73±1.66)、(4.44±1.53)、(4.43±1.78)h;AUC0～12h分别为(4.56±1.32)、(20.90±2.63)、(40.25±3.42)、(4.11±0.60)、(3.28±0.90)μg·h·g-1/μg·h·mL-1。药动学分布呈二室模型。结论:家兔单剂量灌服左氧氟沙星后在眼内各组织中分布较快,且有较高的药物浓度,消除较慢,维持时间较长。     

家兔静注环丙沙星后血液与眼组织分布及其药代动力学研究

研究家兔静注环丙沙星 (CPL X)后血液与眼组织分布及药代动力学参数。用高效液相色谱法测定血液和眼内各组织中药物浓度。结果给药 30 min后泪液、角膜、房水、虹膜 -睫状体、晶状体和玻璃体组织内峰浓度值 (Cmax)分别为 (8.92± 2 .88)、(14 2 .84± 2 5 .0 2 )、(11.0 6± 2 .80 )、(99.32± 10 .6 0 )、(30 .2 8± 1.91)和(8.10± 1.71) μg/ ml或 μg/ g;其血液和各组织中消除半衰期 (T1 /2β)分别为 (1.2 1± 0 .2 3)、(1.4 8± 0 .97)、(1.6 6± 0 .13)、(2 .0 9± 0 .5 1)、(2 .0 1± 0 .4 4 )、(1.5 2± 0 .92 )和 (1.2 1± 0 .6 6 ) h。表明家兔静注 CPL X后能穿透到眼内各组织中。     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.     

Trichinellosis in immigrants in Switzerland

We describe a case of trichinellosis diagnosed at the Division of Infectious Diseases, Hospital of Lugano, in January 2009. This case was associated with a cluster of cases and was traced to the consumption of contaminated meat after a wild boar hunt in Bosnia.