进口与国产齐多夫定胶囊在健康人体的生物等效性

目的研究国产与进口齐多夫定胶囊（抗病毒药）在健康志愿者体内的药代动力学及生物等效性。方法18例健康志愿者单剂量随机交叉口服试验药和对照药齐多夫定胶囊各200mg，用反相高效液相色谱法测定血药浓度，计算其药代动力学参数，评价2制剂的生物等效性。结果试验与参比制剂的主要药代动力学参数Cmax分别为（1．41±0．34），（1．25±0．36）μg·mL^-1；tmax分别为（0．4±0．2），（0．5±0．2）h；t1／2分别为（1．2±0．15），（1．73±0．39）h；AUC0-t分别为（1．64±0．32），（1．66±0．24）μg·h·mL^-1；AUC0-∞分别为（1．69±0．33），（1．72±0．24）μg·h·mL^-1。上述参数经统计学分析无明显差异。结论2种制剂具有生物等效性。     

阿司达莫缓释片在健康人体的药代动力学和相对生物利用度

目的研究阿司达莫缓释片（抗血栓药）在健康人体的药代动力学。方法18例健康男性志愿者随机交叉口服受试制剂（阿司达莫缓释片）或参比制剂（含双嘧达莫片200mg与阿司匹林肠溶片25mg），用高效液相色谱一紫外法测定血浆中双嘧达莫与水杨酸浓度，经DAS软件计算相对生物利用度，并进行生物等效性评价。结果①单剂量受试与参比双嘧达莫：tmax分别为（3．89±0．47），（1．69±0．42）h；Cmax分别为（1．27±0．33），（2．17±0．75）μg·mL^-1；t1／2分别为（8．40±1．92），（4．78±1．13）h；AUC0-t分别为（7．89±2．70），（8．36±3．41）μg·h·mL^-1；AUC0-∞分别为（8．99±3．12），（8．56±3．50）μg·h·mL^-1。受试与参比水杨酸：tmax分别为（2．11±0．53），（4．78±0．81）h；Cmax分别为（0．97±0．47），（0．95±0．48）μg·mL^-1；t1／2分别为（4．22±0．68），（5．46±1．09）h；AUC0-t分别为（4．06±1．65），（3．98±1．73）μg·h·mL^-1；AUC0-t分别为（4．06±1．65），（3．98±1．73）μg·h·mL^-1；AUC0-∞分别为（4．13±1．65），（4．15±1．79）μg·h·mL^-1。②多剂量受试与参比双嘧达莫：tmax分别为（3．94±0．80），（1．90±0．58）h；Cssmax分别为（1．23±0．38），（1．31±0．32）μg·mL^-1；AUCss分别为（7．48±2．72），（7．73±2．62）μ·h·mL^-1。单次给药后，生物利用度双嘧达莫为（97．2±16．7）％、水杨酸为（103．1±9．8）％；多次给药后，双嘧达莫的生物利用度为（96．7±13．4）％。结论2制剂在体内生物作用等效。     

氟罗沙星胶囊在健康人体的药代动力学和生物等效性

目的研究氟罗沙星胶囊（第3代喹诺酮类抗生素）的药代动力学并评价2种国产制剂的生物等效性。方法用随机分组自身对照方法，20例健康男性志愿者单次口服氟罗沙星参比和受试制剂200mg后，用高效液相色谱一紫外法测定血浆中氟罗沙星浓度，用3P97软件进行药代动力学参数的计算及生物等效性评价。结果2种氟罗沙星胶囊在健康志愿者体内的药一时曲线均符合一室开放模型，参比与受试制剂的主要药代动力学参数：Cmax分别为（2．90±0．55），（2．94±0．53）μg·mL^-1；tmax分别为（1．09±0．44），（1．09±0．38）h；t1/2分别为（12．64±1．71），（13．14±1．78）h；AUC0-t分别为（29．86±3．40），（32．81±4．54）μg·h·mL^-1；AUC0-∞分别为（32．54±3．90），（35．70±5．53）μg·h·mL^-1。受试制剂的相对生物利用度为（110．1±11．4）％。结论氟罗沙星的受试制剂和参比制剂在健康人体有生物等效性。     

单剂口服苦参素胶囊后苦参素及其代谢物苦参碱在健康人体的药代动力学

目的研究苦参素胶囊（抗乙肝药）在健康人体的药代动力学。方法10名健康受试者单剂量口服苦参素胶囊600nag，用液相色谱一串联质谱法同时测定血浆中苦参素及其活性代谢物苦参碱的血药浓度，用3P97软件进行数据处理。结果苦参素的血药浓度-时间过程符合一级吸收的一室模型。苦参素和苦参碱的药代动力学参数：Cmax分别为（0．54±0．15），（2．54±0．36）μg·mL^-1，tmax分别为（2.30±1．20），（12．30±2．60）h，AUC0-1。分别为（2．30±0．41），（41．42±6．38）h·μg·mL^-1，t1／2分别为（1．89±0.34），（7．94±0．49）h。苦参素的CIVF与WF分别为（300．20±43．40）L·h^-1和（799．10±239．50）L。结论口服苦参素胶囊经胃肠吸收后，消除较快；而大部分被转化为活性代谢物苦参碱。     

注射用阿莫西林钠/舒巴坦钠(4:1)在健康人体的药代动力学

目的研究注射用阿莫西林钠／舒巴坦钠（4：1）（抗生素）中阿莫西林钠及舒巴坦钠在健康志愿者体内的药代动力学。方法8名健康受试者静脉滴注阿莫西林钠2000mg及舒巴坦钠500mg后，用液相色谱-质谱联用法同时测定血浆中阿莫西林和舒巴坦的浓度。结果血浆中的阿莫西林和舒巴坦的Cmax分别为（105．40±16．42），（49．87±9．62）μg·mL^-1；t1／2分别为（1．68±0．75），（1．77±0．62）h；AUC0-tn分别为（163．44±45．88），（79．66±22．42）μg·h·mL^-1；CL分别为（12．80±3．14），（6．61±1．57）L·h^-1；V2分别为（30．90±14．80），（17．22±7．61）L；MRT分别为：（2．41±0．22），（1．86±0．23）h。结论2种药在体内的药物浓度比约为2：1；12h尿药累积排泄率阿莫西林钠为60％，舒巴坦钠为70％。     

液相色谱-串联质谱法测定缬更昔洛韦血药浓度及其在健康人体的药代动力学研究

目的研究缬更昔洛韦片剂（抗病毒药）在健康人体内的原药缬更昔洛韦及其活性代谢产物更昔洛韦的药代动力学过程。方法20名健康男性受试者单次口服缬更昔洛韦片900mg，用LC—MS／MS测定给药后不同时间血浆中缬更昔洛韦及其活性代谢产物更昔洛韦的浓度，研究缬更昔洛韦与更昔洛韦的药代动力学特征。结果主要药代动力学参数如下。缬更昔洛韦：AUC0-1为（606．83±245．53）μg·h·L^-1；AUC0-∞为（616．52±247．89）μg·h·L^-1；Cmax为（423．56±178．20）μg·L^-1；tmax为（1．15±0．41）h；t1／2为（0．82±0．25）h；MRT0-1为（1．58±0．37）h；MRT0-∞为（1．66±0．38）h；Ka为（2．57±2．53）h^-1；Ke为（0．91±0．24）h^-1；V／F为（1963．85±920．05）L；CIMF为（1688．77±636．77）L·h^-1。更昔洛韦：AUC0-1为：（24．99±7．78）mg·h·L^-1，AUC0-∞为（26．37±7．80）mg·h·L^-1；Cmax为（7．11±1．96）mg·L^-1；tmax为（1．76±0．59）h；t1／2为（3．49±0．96）h；MRT0-1为（4．04±0．80）h；MRT0-∞为（4．81±0．84）h；琏为（1．13±I．20）h^-1；Ke为（0．21±0．07）h^-1；V／F为（178．55±44．82）L；CL／F为（37．33±11．92）L·h^-1。结论本文建立的测定方法，简单、快速、无干扰，适合人体内血药浓度监测和药代动力学研究。     

盐酸曲美他嗪片在健康人体的药代动力学

目的评价盐酸曲美他嗪片（抗心绞痛药）在健康人体的药代动力学。方法24名健康男性志愿者单剂量口服盐酸曲美他嗪片40mg，用液相色谱-串联质谱法测定血药浓度，用DAS软件计算药代动力学参数。结果主要药代动力学参数：Cmax为（126.74±21．42）μg·L^-1，tmax为（1．77±0.64）h。t1／2Ke为（5．90±0．81）h；AUC0-24和AUC0-∞分别为（1209．61±199．93），（1303．221±223。57）μg·h·L^-1。结论单剂量口服曲美他嗪片剂符合一室模型。     

高效液相色谱法测定人血浆中阿莫西林含量

目的：建立反相高效液相色谱法测定血浆中阿莫西林浓度的方法。方法：色谱柱为Waterssunfire C18色谱柱（150mm×4．6mm，5μm），流动相为0．05mol·L。磷酸二氢钾溶液．乙腈（96．2：3．8），用磷酸调至pH=3．0，检测波长210nm。结果：血样中阿莫西林的保留时间约为7．7min，最低定量限为0．2μg·ml-1，在0．2—20．0μg·ml-1范围内呈良好线性，平均方法学回收率为97．36％-99．21％，平均提取回收率为89．21％-92．05％，日内和日间RSD〈5％。健康志愿者口服1．0g阿莫西林后药动学参数Cmax为（15．41±4．56）μg·ml-1；t1／2为（1．24±0．20）h；tmax为（1．56±0．38）h；AUC0—8为（47．69±12．25）μg·ml-1·h；AUC0-∞为（48．68±12．52）μg·ml-1·h。结论：本方法稳定、快捷、灵敏，适用于阿莫西林制剂人体药物动力学研究。     

高效液相色谱-荧光检测法测定萘哌地尔血药浓度及其在健康人体的药代动力学研究

目的建立测定人血清中萘哌地尔（抗高血药）的高效液相色谱-荧光检测法，研究萘哌地尔片剂在健康人体的药代动力学。方法10名健康男性志愿者单次口服萘哌地尔片剂50mg，用高效液相色谱-荧光检测法测定血清中萘哌地尔浓度，用3P87计算其主要药代动力学参数。结果在0．5～100ng·mL^-1内线性良好，日内差≤7．83％，日间差≤9．08％，回收率为98．04％～99．22％；Cmax为（97．65±16．91）ng·mL^-1；tmax为（0．53±0．13）h；t1／tKe为（3．42±0．80）h；AUC0-16为（123．64±31．98）ng·h·mL^-1。结论本方法灵敏、准确，可用于人体药代动力学研究。     

盐酸纳曲酮片在健康人体的药代动力学和相对生物利用度

目的研究进口与国产盐酸钠曲酮（解毒药）在健康人体的生物等效性。方法20名健康志愿者交叉口服受试制剂或参比制剂50mg。用HPLC-MS测定其血药浓度，计算主要药代动力学参数及相对生物利用度，判断其是否有生物等效性。结果在0．10-41．08ng·mL^-1，线性关系良好，最低定量限为0．10ng·mL^-1。受试制剂和参比制剂的药代动力学参数：t1/2分别为（3．59±0．49），（3．76±0．48）h；tmax分别为（1．0±0．4），（1．0±0．5）h；Cmax分别为（16．30±8．31），（15．83±7．17）ng·mL^-1。以AUC0-16计算受试片剂的相对生物利用度为（102．2±13．9）％。2制剂的主要药代动力学参数无显著性差异。结论2种制剂具有生物等效性。     

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.     

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.     

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。     

Polymorphisms in genes involved in neurotransmission in relation to smoking

Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D₁, D₂, and D₄ receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D₃ and D₅ receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.     

Tramadol concentrations in blood and in cerebrospinal fluid in a neonate

Based on blood and cerebrospinal fluid samples collected in a full-term neonate, the penetration of tramadol in the central nervous system is described. Following intravenous administration of tramadol, a lag time of about 4 h was observed until full blood–brain equilibration was achieved. This pharmacokinetic observation is in line with a recent pharmacodynamic evaluation of the central opioid effects of tramadol in adults.     

Disease control in asthmatic children seen in private practice in Switzerland

ABSTRACT

Background: Asthma is the most common chronic childhood disease in Switzerland with a prevalence of 10%. Asthma has a high economic burden accounting for high medical costs. Assessment of disease control is likely to be of help in the implementation of strategies to improve asthma. Therefore, we aimed to evaluate asthma control and therapy regimens among children in private practice.

Methods: We assessed asthma control as well as therapy regimens in 575 asthmatic children in an experience programme in Switzerland by using an abbreviated questionnaire based on the asthma control questionnaire and the child health questionnaire on Visit 1 and Visit 2.

Results: Good asthma control at Visit 1 was only present in 25.7% of asthmatic children. Occasional asthma symptoms, limitation of physical activity, nocturnal awakening and anxiety of the parent was present in 80.5%, 41.2%, 46.8% and 57% of the children, respectively. After adjustment of therapy regimens at Visit 1, mainly by adding a leukotriene receptor antagonist, asthma control was reported to be much better in 53.4% of the children at Visit 2.

Conclusions: As asthma control is inadequately achieved within a major portion of asthmatic children, it is imperative to find measures to improve asthma control and hence, to reduce the burden of disease.