双氯芬酸钠对大鼠足跖肿胀的抑制作用及其与肿胀组织中药物浓 …

目的;观察双氯芬酸欠对鹿角菜所致大鼠足跖肿胀的抑制作用及其与肿胀组织和血浆中药物浓度的关系。方法：足跖皮下注射１％鹿角菜制备大鼠足跖肿胀模型,观察双氯芬酸钠对足跖肿胀的抑制作用,并采用高效液相色谱法测定该模型中足跖肿胀组织和血浆中的双氯芬酸钠浓度,分析其药动学特征。     

阿奇霉素在肺炎患者支气管灌洗液中的浓度测定

目的：观察阿奇霉素在下呼吸道感染患者肺中的浓度。方法：应用微生物法测定肺炎病人血清及支气管灌洗液中阿奇霉素的浓度。结果：患者口服阿奇霉素５００ ｍｇ 后,血清及支气管灌洗液中浓度在４８ ｈ 最高峰值分别是０．３４ μｇ·ｍｌ－ １ 和２ ．２７μｇ·ｍｌ－ １ ,９６ ｈ 时支气管灌洗液浓度和血清浓度分别为０ ．０７ μｇ·ｍｌ－１ 和１ ．３４ μｇ·ｍｌ－１ 。提示肺中浓度明显高于血清浓度。结论：阿奇霉素有较高的组织渗透性。     

双氯芬酸钾的药效研究

用小鼠和大鼠对双氯芬酸钾原粉进行镇痛,抗炎的药效作用及急性毒性评价。方法角叉菜胶致大鼠足跖肿胀法,二甲苯致小鼠耳廓肿胀法,热板法及扭体法。结果：抗炎试验结果显示,单次口服ＤＫ５．０－２０．０ｍｇ．ｋｇ＾－１对角叉菜胶所致大鼠足跖肿胀的抑制作用显著,     

反相高效液相色谱法测定5-氨基水杨酸及其代谢物在人血浆及尿中的浓度

目的：研究５－氨基水杨酸及其代谢物在人血浆及尿中的浓度。方法：反相高效液相色谱法（ＲＰ－ＨＰＬＣ）为测定方法。结果：血浆测定两者线性范围均为０．０８～８．００μｇ·ｍｌ－１，最低检出浓度均为０．０４μｇ·ｍｌ－１，两者平均回收率分别为８７．９３％，９１．４８％，日内ＲＳＤ分别为６．０４％，５．５１％，日间ＲＳＤ分别为７．９８％，４．４３％。５－氨基水杨酸尿浓度测定线性范围为０．５～１０μｇ·ｍｌ－１，最低检出浓度为０．２５μｇ·ｍｌ－１，平均回收率为１０１．８３％，日内ＲＳＤ为１．５７％，日间ＲＳＤ为２．６４％。结论：该测定方法快速，简便，灵敏     

反相高效液相色谱法测定萘普生钠血浆浓度

目的：建立用高效液相色谱法测定萘普生钠血浆浓度的方法。方法：血浆样品在酸性条件下,以１,２二氯乙烷提取,吲哚美辛为内标,采用ＬｉｃｈｒｏｓｏｒｂＣ１８（５μｍ）柱,流动相为甲醇∶醋酸醋酸铵缓冲液（ｐＨ４．５）＝７４∶２６,流速为１．０ｍｌ·ｍｉｎ－１,检测波长３１８ｎｍ,萘普生和内标的保留时间分别为３．３５和４．７１ｍｉｎ。结果：线性范围在１～９０μｇ·ｍｌ－１（ｒ＝０．９９９９,最低检测浓度为０．４μｇ·ｍｌ－１血浆,ＲＳＤ％＜３．５。结论：本方法可用于萘普生钠的药物动力学研究     

双氯芬酸钠在大鼠体内药代动力学的研究

目的：研究双氯芬酸钠在大鼠体内的药代动力学过程。方法：大鼠口服给药后颈静脉插管术采血，用反相高效液相色谱法测定血浆药物浓度。结果：药代动力学过程符合二室模型，Ａ＝６２６４±２７１７μｇ／ｍｌ，α＝１９８２±０６３５·ｈ－１，Ｂ＝４７１２±３３７１μｇ／ｍｌ，β＝０１６３±００５６·ｈ－１，Ｖｄ＝０５７８±０１８４Ｌ，ｔ１／２／β＝４６２２±１３２２ｈ，Ｔｐ＝０２６４±０１１５ｈ。结论：双氯芬酸钠口服易吸收，分布快而广泛     

氨茶碱不同给药方案的血药浓度比较

对氨茶碱不同给药方案进行血药浓度监测,为临床合理用药提供依据。方法：采用ＨＰＬＣ法测定血中不同时间的茶碱浓度,１０２例患者氨茶碱的给药方案分为口服组,静脉滴注组,静脉滴注＋口服组。结果：（１）口服０．２ｇ,ｑ８ｈ,或０．２ｇｔｉｄ的患者血药谷峰浓度在１０～２０μｇ·ｍｌ－１范围分别约占８７％和６５％。（２）静脉滴注０．５ｇ,ｑｄ,或静脉滴注０．２５ｇ,ｑｄ＋口服０．１ｇ,ｔｉｄ的患者血药谷峰浓度在１０～２０μｇ·ｍｌ－１范围分别约占７８％和８２％。（３）口服０．１ｇ,ｔｉｄ或０．２ｇ,ｑｎ的患者血药谷浓度＜１０μｇ·ｍｌ－１,分别约占９３％和８２％。３例发生毒性反应血药浓度均＞２０μｇ·ｍｌ－１。结论：对轻、中度哮喘的治疗和预防应使用较小剂量（０．１ｇ,ｔｉｄ或０．２ｇ,ｑｎ）,维持血药浓度在５～１０μｇ·ｍｌ－１即可。     

高效液相色谱法测定盐酸环丙沙星血药浓度及其药动学研究

采用高效液相色谱法（ＨＰＬＣ）测定盐酸环丙沙星的血药浓度。色谱条件为：紫外检测波长λ２７７ｎｍ；分析柱为ＨＰ－ＲＰ－ＯＤＳＣ１８柱，Φ４．６×２２０ｍｍ；流动相：乙腈∶（溴化四丁基铵０．００８ｍｏｌ·Ｌ－１＋磷酸二氢钾水溶液０．０１１ｍｏｌ·Ｌ－１）＝１４∶８６，配好后磷酸调ｐＨ至２．７４±０．０２。本法血清最低检出浓度０．０１μｇ·ｍｌ－１。对１０名受试者口服５００ｍｇ两种盐酸环丙沙星片后进行药动学和生物利用度研究。药－时曲线经拟合为二室开放模型，其Ｔ１／２β分别为４．６８±０．５３ｈ与４．４０±０．４７ｈ，Ｔｍａｘ分别为１．２８±０．０７ｈ与１．３３±０．０７ｈ，Ｃｍａｘ分别为６．４４±０．６１（μｇ·ｍｌ－１）与５．８８±０．４０（μｇ·ｍｌ－１），ＡＵＣ分别为１９．８８±１．８３（μｇ·ｈ－１·ｍｌ－１）和１９．２４±１．０８（μｇ·ｈ－１·ｍｌ－１）。供试品片剂的相对生物利用度为１０３．３２±４．８１％（９９．５８±４．６３％，经含量校正），经统计分析两种制剂具有生物等效性。     

进口和国产索他洛尔片剂的相对生物利用度研究

目的：本文对进口和国产索他洛尔片剂在１２名男性健康志愿者中的药物动力学和相对生物利用度进行了研究。方法：建立了一个检测血清中索他洛尔浓度的反相高效液相色谱－荧光检测法。结果：单剂量口服索他洛尔１６０ｍｇ后的血药浓度数据用３Ｐ８７药物动力学程序进行模型拟合，国产片剂ＡＵＣ、Ｃｍａｘ、Ｔｍａｘ、Ｔ１／２分别为１６．２±３．６ｈ·μｇ·ｍｌ－１，１．２±０．２μｇ·ｍｌ－１，２．１±０．７ｈ，１７．０±７．２ｈ；进口片剂ＡＵＣ、Ｃｍａｘ、Ｔｍａｘ、Ｔ１／２分别为１５．９±３．５ｈ·μｇ·ｍｌ－１，１．２±０．４μｇ·ｍｌ－１，２．１±０．６ｈ，１８．６±９．４ｈ。国产片剂的相对生物利用度为１０３．５％。结论：两种片剂的所有药动学参数经统计学（ＳＰＳＳ软件）处理差异均无显著性（Ｐ＞０．０５）。     

反相高效液相色谱法测定5—氨基水杨酸及其代谢物在人血浆 …

研究５－氨基水杨酸及其代谢物在人血浆及尿中的浓度。方法：反相高效液相色谱法为测定方法。结果：血浆测定两者线性范围为０．０８－８．００μｇ．ｍｌ＾－１，最低检出浓度均为０．０４μｇ．ｍｌ＾－１，两者平均回收率分别为８７．３％，９１．４８％，日内ＲＳＤ分别为６．０４％，５．５１％，日间ＲＳＤ分别为７．９８％，４．３％。     

Carrageenan-induced oedema in the rat paw - histamine participation

Participation of histamine in the inflammatory reaction produced by carrageenan was studied. Mepyramine did not influence the course of the inflammatory reaction. In contrast to when mepyramine was used, there was a significant inhibition of carrageenan oedema when cimetidine was used. Pretreatment of animals with compound 48/80 significantly reduced the oedema formation. Neither mepyramine nor cimetidine reversed the inhibition of rat paw swelling produced by histamine liberators. It is concluded that histamine participates in carrageenan oedema via its H2-receptors and that the anti-inflammatory effect of compound 48/80 is not connected with the 'anti-inflammatory' action of liberated histamine.     

Haemostatic imbalance following carrageenan-induced rat paw oedema

Carrageenan-induced rat paw oedema is a widely used model to investigate the physiopathology of an acute local inflammation. Recently, much attention has been focused on the link between haemostasis and inflammation, and on the impact that inflammation might have on thrombotic events. It is known that the systemic response to inflammation is the "acute phase reaction" that represents a highly complex reaction of the organism to a variety of injuries, aimed to restore homeostasis; one important feature of the acute phase reaction is the hepatic synthesis of proteins involved in the coagulation cascade. Much attention has been focused on the role that systemic inflammation might have on thrombotic events, while there is not much information on the role played by an acute local inflammation on haemostasis, that can lead toward a pro-thrombotic state. The present study was conducted to evaluate the haemostatic balance in the early and the late phase of carrageenan-induced rat paw oedema; i.e. at 3 h, when paw inflammation is maximally expressed, and 24 h following carrageenan injection, when there is an almost complete absence of local inflammatory symptoms. We found that in inflamed animals, 24 h following oedema induction, there was an increase in plasma fibrinogen levels, antithrombin III activity and serum interleukin-6 levels, concomitant to a shortened prothrombin time and to an increased platelet responsiveness to ADP. Furthermore, in inflamed tissues at 3 h there was an increase in antithrombin III proteic expression. Our results demonstrate that a haemostatic imbalance occurs following carrageenan-induced rat paw oedema.     

Serotonin-induced paw edema in the rat: Pharmacological profile

• 1.1. Serotonin (5-HT) induced a linear increase in paw weight in rats within 1hr of an intraplantar injection (50μ1 vol) over a concentration range of 0.005–0.2mg/ml. At the 0.2 mg/ml concentration, a 16-fold increase in paw weight was observed as compared to saline-injected controls.
• 2.2. Serotonin antagonists, such as LY53857, were the most effective antagonists of 5-HT induced paw swelling, producing near complete antagonism and an approximate ED₅₀ of 0.1 mg/kg. A mixed 5-HT/histamine antagonist, cyproheptadine, also produced a nearly complete inhibition of the 5-HT response with an approximate ED₅₀ of 1.3 mg/kg.
• 3.3. Dopamine agonists (pergolide, quinpirole), yohimbine, dexamethasone and nifedipine also produced a significant degree of antagonism of the 5-HT response.
• 4.4. Clonidine, prazocin, chlorpheniramine, cimetidine, various dopamine antagonists, imipramine, cyclosporine A, piroxicam and superoxide dismutase were all ineffective at altering the paw swelling response to 5-HT.

     

The pharmacology of arachidonic acid-induced rat paw edema

Arachidonic acid (AA) injected into hindpaws of Lewis rats produces a severe edematous response. Treatment with corticosteroids (dexamethasone, prednisolone), dual inhibitors of arachidonate metabolism (phenidone, SK & F 86002), anti-histamine/serotonin agents (chlorpheniramine, cyproheptadine) and a gold compound (auranofin) inhibited AA-induced edema. In contrast, administration of high doses of cyclooxygenase inhibitors (indomethacin, piroxicam, naproxen, ibuprofen, meclofenamic acid and tiflamizole) did not affect AA-induced hind paw edema. The involvement of lipoxygenase products and mast cell mediators in the edematous response to arachidonic acid render this model potentially useful for studying antiinflammatory agents with a mechanism of action different from that of cyclooxygenase inhibitors.     

Mediators of the inflammation induced in the rat paw by carrageenin

1. The time course of oedema formation in rats caused by injection of carrageenin into the paw was followed for 5.5 hours. Intact or adrenalectomized rats which had previously been injected with ellagic acid or saliva to reduce considerably the concentration of blood kininogens, or with methysergide to antagonize 5-hydroxytryptamine (5-HT) showed a reduced inflammatory response. It was concluded that kinins and 5-HT contributed significantly to oedema formation during this period.2. Mepyramine alone had no effect on oedema formation, but in combination with ellagic acid treatment, with or without methysergide, it caused a reduction suggesting that histamine played a minor role in oedema formation during the first 3 hours.3. Vascular permeability studies indicated that injection of ellagic acid did not interfere with the normal responses in skin to intradermal injections of histamine, 5-HT, bradykinin or compound 48/80. Mepyramine and methysergide, at the doses used in the carrageenin experiments, completely antagonized histamine and 5-HT, respectively, and did not affect the skin responses of bradykinin.4. Treatment in vivo with ellagic acid or rat saliva was equally effective in reducing plasma kininogen concentrations by an amount equivalent to more than 10 times the quantity of substrate 1 measured by Gautvik & Rugstad (1967).5. Rat saliva, but not ellagic acid, lowered complement levels by approximately 20%.     

The inflammatory reaction induced by formalin in the rat paw

The involvement of bradykinin and some other inflammatory mediators in formalin-induced oedema and plasma extravasation was examined. Formalin was injected in rat paws at two doses, 1.75% or 5%. The lower dose induced the development of an immediate oedema associated with a progressive accumulation of ¹²⁵I-labelled albumin in the paws. These changes were suppressed by pretreatment with capsaicin or xylocaine. They were abolished by RP67580, a NK₁ receptor antagonist, and increased by phosphoramidon or diprotin A. They were not affected by HOE140, a bradykinin B₂ antagonist, captopril, methysergide, mepyramine, indomethacin, ketoprofen or l-N ^G-nitroarginine. The higher dose of formalin induced a swelling of the paws which took place in two phases associated with two periods of increase in vascular permeability. This oedema was reduced by pretreatment with capsaicin but not with xylocaine. It was reduced by RP67580 injected before or 30 min after formalin. It was inhibited by mepyramine, methysergide, indomethacin and NS-398, a cyclooxy-genase-2 inhibitor. It was not modified by HOE140. Its development was similar in normal and kininogen-deficient rats. We concluded that formalin administered at a low dose induces an oedema which mainly results from a neurogenic inflammation mediated by neuropeptides such as substance P. At higher doses, formalin induces an oedema which mainly depends on the release of substance P, prostanoids, 5-hydroxytryptamine and histamine. Bradykinin plays no significant role in the vascular changes whereas this peptide has been reported to participate in the stimulation of nociceptive afferent neurons. This discrepancy could be explained by a difference in the threshold of stimulation of the nociceptive neurons and that of the cells of the vascular walls, or by a formation of kinins in close contact of the neurons. Received: 29 June 1998 / Accepted: 20 November 1998     

Modulation of inflammatory paw oedema by cysteamine in the rat.

Cysteamine, a potent somatostatin depletor, was used in the present study to investigate the role of endogenous somatostatin in acute peripheral inflammation. The acute inflammation was induced by intraplantar injection of carrageenan (1%), histamine (5 micromol), or formalin (2.5%) in the rat hind paw. The induced inflammation and the formation of oedema were determined by measurement of the paw thickness. Given subcutaneously (s.c.) 1 h before carrageenan, cysteamine caused significant, dose-dependent and long-lasting inhibition of rat paw oedema induced by carrageenan. At doses of 12.5, 25, 50 or 100 mg kg (-1), cysteamine significantly inhibited the carrageenan-induced paw oedema at 4 h by 52.3, 40, 40.7 or 26.3%. Cysteamine given at 300 mg kg (-1), a dose well known to deplete tissue somatostatin, reduced oedema by only 16.2% vs control values. Significant inhibition of the carrageenan-induced rat paw oedema was still evident 24 h post-injection at cysteamine doses of 12.5, 25, 50 or 100 mg kg (-1). Given s.c. at 300 mg kg (-1), 4 h prior to carrageenan, cysteamine decreased rat paw oedema at 4 h by 14.9%. Cysteamine (300 mg kg (-1)), 4 h beforehand, had little modulatory effect on the oedema induced by formalin (2.5%) but reduced that caused by intraplantar histamine (5 micromol). The anti-oedematogenic effect of indomethacin, but not that of the selective COX-2 inhibitor celecoxib, was less marked in rats pre-treated with cysteamine at 300 mg kg (-1). Cysteamine (0.3 microg- 0.3 mg paw (-1)) co-administered with carrageenan was devoid of anti-inflammatory effect and even promoted inflammation at low concentrations. Cysteamine given locally alone induced slight paw oedema. These data indicate that systemic cysteamine possesses potent and long-lasting anti-inflammatory effects and modulates the anti-inflammatory effect of cyclooxygenase inhibitors in a model of peripheral inflammation in the rat. The effect of cysteamine is likely to be mediated via central action.