甲硝唑大鼠肠吸收实验研究

目的考察甲硝唑在大鼠不同肠段的吸收动力学特征、吸收部位及吸收机制,为其结肠定位缓控释制剂的设计提供理论依据。方法采用大鼠在体灌流肠吸收实验,考察了甲硝唑的吸收部位和吸收动力学特征。结果甲硝唑在大鼠肠道内无特定吸收部位,各肠段吸收速率常数按十二指肠、空肠、结肠、回肠顺序依次上升,吸收速率常数分别为0.078、0.136、0.155、0.168/h。在2～20μg/ml的浓度范围内,甲硝唑的吸收量与浓度有良好的线性关系。结论甲硝唑在大鼠全肠段均有吸收,吸收符合一级动力学特征,吸收机制为被动扩散,适于制备结肠定位缓控释制剂。     

外翻肠囊法考察环孢素在大鼠各肠段的吸收特性

目的 研究环孢素A(CsA)在大鼠各肠段的吸收特征. 方法 采用大鼠体外肠外翻模型,用高效液相色谱(HPLC)法检测CsA,计算CsA吸收速率参数. 结果 CsA在大鼠各肠段吸收较差,吸收速率常数按十二指肠、空肠、回肠、结肠顺序依次下降,分别为6.646 9,4.917 9,4.262 7,2.686 1 min^-1. 结论 CsA在大鼠各肠段吸收呈一级动力学. 该方法 准确、灵敏度高、特异性强,适用于CsA肠吸收特征的研究.     

辛伐他汀大鼠肠吸收动力学研究

目的:研究辛伐他汀在大鼠各肠段的吸收动力学特征。方法:采用大鼠在体肠段回流实验,主要从吸收部位、药物浓度、pH值方面对辛伐他汀的肠段吸收特性进行研究。结果:辛伐他汀在大鼠肠道内无特定吸收部位,各肠段吸收速率常数按十二指肠、结肠、空肠、回肠顺序依次下降,分别为0.03365、0.03190、0.02942、0.02563h-1。辛伐他汀在1.0～20.0μg·mL-1浓度范围内药物吸收量呈线性关系;在pH5.0～7.4内药物吸收不受pH值影响。结论:辛伐他汀在大鼠全肠段均有吸收,吸收符合一级动力学特征,吸收机制为被动扩散,适于制备日服1次缓释给药系统。     

香青兰黄酮类化合物的大鼠在体肠吸收

目的:研究香青兰总黄酮在大鼠各肠段的吸收动力学特征。方法:采用大鼠在体肠灌流模型,利用HPLC法测定灌流液中田蓟苷的浓度,研究田蓟苷和香青兰总黄酮在大鼠各肠段的吸收特性。结果:香青兰总黄酮中田蓟苷在大鼠各肠段的吸收速率常数Ka值按结肠、空肠、十二指肠、回肠顺序依次分别为5.7651×10-2,4.4081×10-2,4.3873×10-2,3.9899×10-2;田蓟苷在大鼠各肠段的吸收速率常数Ka值按十二指肠、回肠、空肠、结肠顺序依次分别为6.7897×10-2,6.3018×10-2,5.8011×10-2,5.6765×10-2。结论:田蓟苷单体与香青兰总黄酮中田蓟苷在大鼠各肠段的吸收特征相一致,二者在大鼠小肠段不同部位的吸收均不存在差异。     

石杉碱甲大鼠在体肠吸收动力学研究

目的研究石杉碱甲在大鼠小肠及各肠段的吸收动力学特征.方法采用大鼠在体方式对石杉碱甲进行了大鼠小肠及各肠段的吸收动力学研究;采用HPLC法测定石杉碱甲在大鼠体内肠吸收循环液中的药物浓度;采用UV法测定循环液中酚红浓度.结果石杉碱甲在小肠中吸收较好且没有特定吸收部位,各肠段吸收速率按十二指肠、空肠、回肠、结肠依次为0.001 0、0.000 9、0.001 1、0.000 9 h-1.结论结肠的吸收速率常数与小肠段相近,药物在肠道的吸收呈现一级吸收动力学,吸收机制为被动吸收,提示适于制备日服一次(24 h)缓释给药制剂.     

尼莫地平大鼠在体肠吸收动力学

目的研究尼莫地平在大鼠各肠段的吸收动力学特征。方法采用大鼠在体肠段灌流实验 ,主要从吸收部位、药物浓度、pH值等 3方面对尼莫地平的肠段吸收特性进行研究。结果尼莫地平在大鼠肠道内无特定吸收部位 ,各肠段吸收速率常数按十二指肠、空肠、结肠、回肠顺序依次下降 ,吸收速率常数分别为 0 0 6 87、0 0 6 2 0、0 0 5 97、0 0 4 89h-1。在 4 8～ 14 3μmol·L-1浓度内药物吸收量与浓度呈线性关系 ;在 pH 5 0～ 7 4内药物吸收不受 pH值影响。 结论尼莫地平在大鼠全肠段均有吸收 ,吸收符合一级动力学特征 ,吸收机制为被动扩散 ,适于制备日服 1次缓释给药系统     

尼扎替丁大鼠肠吸收动力学研究

目的 研究尼扎替丁大鼠肠吸收的吸收动力学特征.方法 采用大鼠离体和在体肠吸收模型,以高效液相色谱法测定尼扎替丁的浓度.结果 尼扎替丁在肠道各部位的吸收速率按十二指肠、空肠、回肠、结肠的顺序下降,吸收速率常数分别为(0.0699±0.0033)/h、(0.0629±0.0018)/h、(0.0614±0.0026)/h、...     

利巴韦林大鼠肠吸收动力学

目的研究利巴韦林在大鼠各肠段的吸收动力学特征。方法应用大鼠在体灌流肠吸收实验考察其吸收动力学 ;采用HPLC法测定利巴韦林在大鼠体内肠吸收回流液中的药物浓度 ;采用UV法测定回流液中酚红浓度的变化。结果利巴韦林在小肠中上部吸收较好 ,吸收速率按十二指肠、空肠、回肠、结肠依次下降 ,吸收速率常数依次为 0 0 970 0、0 0 15 0 0、0 0 0 110、0 0 0 0 0 5h-1;回流液中吸收药物的量与利巴韦林的浓度成正比。结论利巴韦林在肠道的吸收呈一级吸收动力学特征 ,吸收机制为被动吸收 ;主要吸收部位为十二指肠和小肠上部 ,结肠几乎无吸收 ;提示该药适合制成日服 2次的缓释制剂     

法莫替丁大鼠在体小肠吸收动力学研究

应用大鼠在体肠吸收实验方法研究了法莫替丁各肠段的吸收动力学特征。实验表明 :法莫替丁在肠道各部位的吸收速率按十二指肠、空肠、回肠、结肠顺序下降 ,吸收速率常数分别为0 0 5 0 8,0 0 44 6 ,0 0 415 ,0 0 2 87h-1。药物在肠道内的吸收呈现一级吸收动力学过程 ,其吸收机制为被动扩散     

洛索洛芬钠大鼠在体肠吸收动力学研究

目的:研究洛索洛芬钠大鼠在体肠吸收动力学,为剂型设计提供依据。方法:采用大鼠在体肠灌流方法,采用高效液相色谱法-紫外检测器测定洛索洛芬含量,取麻醉后大鼠的十二指肠、空肠、回肠和结肠段作为受试肠段建立在体肠灌流模型,计算洛索洛芬的吸收速率常数和吸收百分率。结果:洛索洛芬在大鼠各肠段吸收百分率和吸收速率常数均无显著性差异(P>0.05),无特异吸收部位。洛索洛芬在不同质量浓度及pH范围内的肠吸收速率常数基本不变。结论:洛索洛芬大鼠肠吸收为一级动力学过程,各肠段均有吸收,吸收机制为被动扩散,适合制成缓控释制剂。     

Effects of non-steroidal anti-inflammatory drugs on isolated human polymorphonuclear leukocytes (PMN): chemotaxis, superoxide production, degranulation and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) receptor binding

1. We have examined the effects of tolmetin and meclofenamate on isolated human PMN functions under FMLP stimulating conditions. 2. In a dose dependent manner, tolmetin and meclofenamate inhibited all PMN functions, except that tolmetin stimulated PMN chemotaxis. 3. Meclofenamate was much more potent than tolmetin as an inhibitory agent. 4. We also conducted competitive receptor binding assays for tolmetin, meclofenamate and ibuprofen on the FMLP receptor. 5. All three NSAID inhibited FMLP binding in a dose dependent manner with the potency order being meclofenamate greater than ibuprofen greater than tolmetin.     

传递体作为酮康唑经皮渗透载体的体外研究

目的:制备酮康唑传递体,测定其含量;研究酮康唑传递体的经皮渗透促进作用。方法:用旋转蒸发法制备酮康唑传递体,反相HPLC法测定酮康唑的含量。采用改进的franz扩散池体外经皮渗透实验。以兔皮背部皮肤为透皮屏障,紫外分分光光度法测定普通纳米脂质体、含有表面活性剂胆酸钠酮康唑传递体(KCZ TF)、含3%的双戊烯(3%DP)和3%的氮酮(3%AZ)对酮康唑的促透效果。结果:制得酮康唑传递体。各种促进剂对酮康唑的促透效果顺序为:传递体> 3%双戊烯>3%氮酮>普通纳米脂质体。结论:实验证明,传递体对酮康唑具有良好的促透作用,与其它促透剂相比具有显著差异(P<0.05)或极显著的差异(P< 0.01)。     

Pharmacokinetics of tolmetin with and without concomitant administration of antacid in man

Summary The purpose of this study was to determine whether a concomitant single dose of antacid or multiple doses of antacid administered prior to, and with tolmetin, alter the pharmacokinetics of tolmetin when the drug was administered as a commercially available tablet containing tolmetin sodium. The possible effects of the antacid on plasma concentrations and urinary excretion of tolmetin and its major metabolite were evaluated following administration of: (a) tolmetin sodium alone; (b) antacid four time a day for three days prior to a single dose of tolmetin sodium, with continuation of the antacid during the day tolmetin was given; and (c) co-administration of single doses of tolmetin sodium and antacid. The twenty-four subject study was of the crossover type. There were no significant differences among treatment means for: (i) peak plasma concentrations of both tolmetin and metabolite, (ii) AUC 0–8 h and AUC 0- for both tolmetin and metabolite, (iii) time to peak plasma concentration for both tolmetin and metabolite, (iv) plasma concentrations of both tolmetin and the metabolite at all sampling times (except for tolmetin at 2 h), (v) renal clearance of both tolmetin and its metabolite, and (vi) the amount of metabolite excreted in the 0–24 h urine. There were small, but significant, differences among amounts of tolmetin excreted in the 0–24 h urine. Semilogarithmic plots of both tolmetin and metabolite plasma concentrations past the peak concentrations were curved over the entire 8-h observation period; although the elimination half-life of tolmetin has been reported to be about one hour, the half-life most probably exceeds 2.6 h in most subjects. The results of this study indicate a lack of a significant drug-drug interaction between the non-steroidal anti-inflammatory agent, tolmetin sodium, and a commonly used antacid, which is a mixture of magnesium and aluminium hydroxides.     

甲基斑蝥胺在大鼠胃肠道的吸收动力学

目的研究甲基斑蝥胺(MCD)在大鼠胃及肠道的吸收动力学特征。方法采用封闭灌注技术进行原位胃灌注吸收研究,在体循环法考察小肠全肠段吸收,采用单向肠灌流技术进行不同肠段吸收研究,建立HPLC法测定MCD的浓度,考察MCD大鼠胃肠吸收特征及吸收机制。结果 116.34mg·L~(-1)MCD在十二指肠、空肠、回肠、结肠及胃中的吸收速率常数(K_a)分别为(0.0635±0.0091)、(0.0687±0.0008)、(0.0315±0.0009)、(0.0399±0.0009)和(0.0033±0.0001)min~(-1),不同药物浓度59.55、116.34、204.15mg·L~(-1)时胃及空肠中的K_a分别为(0.0031±0.0001)、(0.0033±0.0001)、(0.0031±0.0001)min~(-1)及(0.0667±0.0010)、(0.0687±0.0008)、(0.0705±0.0011)min~(-1);在空肠不同pH值(5.0,6.2,7.4)时K_a分别为(0.0801±0.000 9)、(0.0783±0.0009)、(0.0758±0.0009)min~(-1)。MCD在胃中吸收很弱;在空肠、十二指肠、结肠和回肠中均有一定吸收,在空肠吸收最好,在肠中吸收呈一级动力学过程,吸收机制为被动扩散。MCD溶液浓度及pH值对其肠吸收速率无显著影响(P>0.05)。结论 MCD属于生物药剂学分类系统Ⅰ类药物。     

Nasal delivery of progestational steroids in ovariectomized rabbits. II. Effect of penetrant hydrophilicity

The influence of penetrant hydrophilicity on nasal pharmacokinetics and systemic bioavailability was studied in ovariectomized female New Zealand White rabbits. The systemic bioavailability of progesterone derivatives with one hydroxy (17--hydroxypro-gesterone, HP), two hydroxy (cortexolone, CT), and three hydroxy (hydrocortisone, HC) groups were compared to progesterone, in separate crossover studies, following i.v., oral, and nasal administrations. Nasal administration was accomplished using an immediate-release nasal spray formulation and a controlled-release nasal device. The rank order of systemic bioavailability after nasal spray was HP > P > CT > HC (97.10, 82.52, 71.99 and 60.90%, respectively), which correlates in a hyperbolic pattern with the nasal mucosa partition coefficients of the drugs. The controlled-release nasal device achieved a more prolonged and steady plasma level of drug than the other routes of administration. The systemic bioavailabilities of progesterone and its hydroxy derivatives after nasal administration were all significantly greater (P < 0.01) than those after oral administration (P 7.87%; HP 5.93%; CT 5.88%; HC, 2.67%). The results of this investigation demonstrate that the extent of nasal absorption is influenced by both the mode of nasal administration and the hydrophilicity of the penetrant, as expressed by the nasal mucosa partition coefficient.     

Tolmetin uptake into inflamed tissue in the rat

Concentrations of the antiinflammatory agent tolmetin have been measured by HPLC in inflamed and non-inflamed rat tissues after oral administration of tolmetin sodium dihydrate in solution (100 mg free acid/kg) and after topical administration of tolmetin (Tolectin gel, 1 g of a 5% gel, 250 mg free acid/kg). After oral administration of tolmetin, there was marked localisation of the drug in inflamed rat paws. Concentrations of tolmetin were significantly greater in inflamed paws than those in non-inflamed paws at each time studied (e.g. at 3 h after dosing, inflamed paw 30.5 micrograms/g, non-inflamed paw 14.9 micrograms/g). After a single topical application of tolmetin gel to the shaved backs of rats, tolmetin was well absorbed percutaneously into the non-inflamed dorsal muscle. After repeated topical application of tolmetin gel to the shaved backs of rats, daily for 4 consecutive days, concentrations of tolmetin (total micrograms/paw) similar in inflamed paws and in non-inflamed paws. After topical administration of tolmetin gel to rat paws, tolmetin was transported from treated paws to untreated paws, e.g. from non-inflamed paws to inflamed paws and vice versa. These studies showed that tolmetin applied topically reaches inflamed tissues in concentrations that exceed those in plasma.     

Site of analgesic action of a non-steroidal, anti-inflammatory drug, tolmetin sodium, in rats.

1 The site of the analgesic action of tolmetin sodium was investigated by use of the acetic acid writhing test in rats. 2 Tolmetin sodium was administered to the rat between 15 and 60 min after intraperitoneal injection of 1 ml of a 1% acetic acid aqueous solution. Number of writhing was counted for 20 min beginning from 60 min after acetic acid injection. 3 When the rat was given tolmetin sodium 5 mg/kg orally, a relatively large quantity of tolmetin was found in the peritoneal exudate and there was a rough correlation between anti-writhing activity and the exudate tolmetin content. 4 Anti-writhing ED50 of tolmetin sodium was 1.42 (0.82-2.91) and 92.0 (57.0-140) microgram/kg when given intraperitoneally and intravenously, respectively, and the potency ratio of intraperitoneal to intravenous tolmetin sodium was 40.0 (18.5-80.2). This potency ratio for salicylic acid and morphine hydrochloride was 19.4 and 1.0, respectively. 5 When equipotent doses ( 5 microgram/kg i.p.; 200 microgram/kg i.v.) of tolmetin sodium were administered to the rat, the plasma tolmetin level after the intraperitoneal administration was less than one-fortieth that after the intravenous administration during the counting time of 20 min, while both the peritoneal exudate contents of tolmetin were nearly equal. 6 From these results, it is concluded that the site of anti-writhing action of tolmetin sodium is in the peritoneum and that tolmetin sodium produces its anti-writhing action mainly by a peripheral mechanism in the rat.     

几种酶抑制剂对胰岛素肠道吸收的影响几种酶抑制剂对胰岛素肠道吸收的影响

目的研究酶抑制剂对胰岛素在大肠和小肠吸收的影响,初步探讨酶抑制剂在肠道各段的作用机制。方法采用原位肠袢法,设计肠道冲洗实验,测定胰岛素肠道吸收后的降血糖效应和血药浓度。结果胰岛素单用于小肠袢或大肠袢时,冲洗实验前后均无降血糖效应。与酶抑制剂合用时,冲洗实验前,小肠段无降血糖效应,冲洗实验后,小肠段降血糖效应有所提高;冲洗实验前后,大肠段均产生明显的降血糖效应。酶抑制剂作用与其种类、应用浓度和不同区段内蛋白水解酶的活性有关;各种酶抑制剂提高胰岛素降血糖效应的顺序为:亮肽素>甘氨胆酸钠>杆菌肽>抑氨肽酶素B>胱蛋白;其中甘氨胆酸钠和杆菌肽还具有渗透促进作用。结论合用酶抑制剂能显著改善胰岛素在大肠处的吸收。     

几种吸收促进剂和酶抑制剂对胰岛素结肠吸收的影响

以胰岛素为模型药物，分别采用体外、在体和体内的方法进行吸收促进剂或酶抑制剂的筛选。结果表明，体外试验中，同一浓度的不同吸收促进剂或酶抑制剂促进胰岛素结肠黏膜渗透的强弱顺序为：Laureth9〉Brij78〉SDC〉STGC〉STC；大鼠在体试验表明，单用胰岛素无降血糖效果，含不同吸收促进剂或酶抑制剂的胰岛素溶液降血糖效果的强弱顺序依次为：Laureth9〉SDC〉Brij78〉STC〉sTGc〉SLC〉BTC。正常大鼠灌胃给予含促进剂或抑制剂组合的胰岛素胶囊，其降血糖效果的强弱顺序为：1％Bdj78＋1％Laureth9〉1％SDC＋1％Laureth9〉1％Bdj78＋1％SDC。