心痛定片剂与滴丸的人体生物利用度及药代动力学的研究

本文采用高压液相色谱法测定心痛定片剂与滴丸的人体血药浓度。流动相：甲醇（色谱纯）─磷酸盐缓冲液（６０：４０），紫外检测波长２３５ｎｍ，以片剂为标准制剂，滴丸的相对生物利用度为１２２．０％。对片剂与滴丸的ＡＵＣ、Ｃｍａｘ、Ｔｍａｘ作ｔ检验，结果二者之间Ｃｍａｘ、Ｔｍａｘ有显著性差异（Ｐ＜０．０５），ＡＵＣ无显著差异（Ｐ＞０．０５），结果表明滴丸较片剂优良。     

头孢氨苄片的人体生物利用度研究

杜实验采用反相高效液相色谱法，比较了１０名健康志愿者单剂量口服自制头孢氨苄片剂０．５ｇ和等剂量的市售头孢氨苄胶胶囊的生物利用度。结果表明：二种剂型Ｔｍａｘ，Ｃｍａｘ，ＡＵＣ均无显著性差异（Ｐ＞０．０５），片剂与胶囊的相对生物利用度Ｆ＝９５．９７５％。     

盐酸曲普利啶胶囊人体失物利用度研究

目的：研究盐酸曲普利啶胶囊在正常人体的相对生物利用度。方法：采用反相高效液相色谱法测定１０名志愿者单剂量口服５ｍｇ盐酸曲普利啶胶囊和片剂后的血药浓度,计算二者的药动学参数及相对生物利用度。以Ｃｍａｘ、ＡＵＣ０等为指标,用双单侧Ｔ检验法及（１２ａ）置信区间法分析两种制剂的生物等效性。结果：二者药时曲线用一室模型拟合,统计结果表明,Ｃｍａｘ等春数无显著性差异（Ｐ＞０．０５）。结论：盐酸曲普利啶胶囊与片剂生物等效,胶囊的生物利用度为９８．２８±５．４３％。     

法莫替丁冲剂在健康人中的生物利用度及药动学研究

本实验采用反相高效液相色谱法，比较了１０名健康志愿者单剂量口服法莫替丁冲剂及等剂量片剂的生物利用度。结果表明：二种剂型的Ｔｍａｘ，Ｃｍａｘ，ＡＵＣ均无显著性差异（Ｐ〉０．０５）。冲剂相对于与片剂的相对生物利用度Ｆ＝１０１．９０。     

盐酸曲普利啶胶囊人体生物利用度研究

目的：研究盐酸曲普利啶胶囊在正常人体的相对生物利用度。方法：采用反相高效液相色谱法测定１０名志愿者单剂量口服５ｍｇ盐酸曲普利啶胶囊和片剂后的血药浓度，计算二者的药动学参数及相对生物利用度。以Ｃｍａｘ、ＡＵＣ０－∞等为指标，用双单侧Ｔ检验法及（１－２α）置信区间法分析两种制剂的生物等效性。结果：二者药时曲线用一室模型拟合，统计结果表明，Ｃｍａｘ等参数无显著性差异（Ｐ〉０．０５）。结论：盐酸曲普利啶胶     

比较氧氟沙星两种片剂在健康志愿者体内的药物动力学

本实验采用反相高效液相荧光分析法，比较了８名健康志愿者单剂量口服两种氧氟沙星片剂后的药物动力学和生物利用度。血药浓度经时过程用ＣＡＰＰ程序包在计算机上拟合为二房室模型，试验片的相对生物利用度Ｆ为１００．１２％，经统计分析，二种片剂的Ｔｍａｘ，Ｃｍａｘ和ＡＵＣ均无显著性差异（Ｐ＞０．０５），可认为二种片剂具有生物等效性。     

两种不同基质环丙沙星栓在家兔体内的药物动力学研究

研制了两种不同基质的环内沙星栓剂，并对其在家兔体内的药物动力学与市售片剂进行了比较。实验表明，两种栓剂的Ｃ＿（ＰＫ），ＡＵＣ值等均明显高于片剂（ｐ＜０．００１），预示可以通过改变给药途径提高环丙沙星的生物利用度。     

国产及进口盐酸噻氯匹啶片药代动力学及人体相对生物利用度

正常健康志愿者１０名（均为男性）口服国产和进口盐酸噻氯匹啶片剂两种制剂（５００ｍｇ）进行药代动力学和相对生物利用度研究。用高效液相色谱法测定血浆中盐酸噻氯匹啶含量,并以３ｐ９７实用药代动力学程序处理实验数据。实验结果表明,口服国产和进口盐酸噻氯匹啶片剂的血药浓度—时间曲线均符合二房室模型,两种制剂的Ｃｍａｘ分别为１８３４±５１０．７及２０１９±５６６．７μｇ／Ｌ;Ｔｐ分别为１．７５±０．７５及２．００±０．７０ｈ;ＡＵＣ分别为６８１５±１４９３及７００８±１３３０μｇ／（Ｌ·ｈ）。经配对ｔ检验,两者的药动学参数均无显著性差异（Ｐ＞０．０５）。方差分析和双单侧检验结果表明,两者具有生物等效性。国产盐酸噻氯匹啶相对生物利用度为９７．０３±８．１１％。     

盐酸特拉唑嗪胶囊人体生物利用度及药物动力学研究

目的：对盐酸特拉唑嗪胶囊的人体内生物利用度进行研究。方法：单剂量口服盐酸特拉唑嗪胶囊和片剂２ｍｇ。血药浓度采用ＨＰＬＣ测定，数据用３Ｐ８７计算药动学参数。结果：盐酸特拉唑嗪胶囊剂的药动学参数：Ｋａ为８．２±４．０ｈ－１，Ｔ１／２为８．２±２．５ｈ，Ｔｍａｘ为０．６１±０．１１ｈ，Ｃｍａｘ为４３．５±８．５ｎｇ·ｍｌ－１，ＡＵＣ为３６７．４±３４．６ｎｇ·ｈ·ｍｌ－１；盐酸特拉唑嗪片剂的药动学参数：Ｋａ为６．４±７．４ｈ－１，Ｔ１／２为７．４±２．１ｈ，Ｔｍａｘ为０．９±０．４ｈ，Ｃｍａｘ为４３．１±４．８ｎｇ·ｍｌ－１，ＡＵＣ为３７１．３±４４．４ｎｇ·ｈ·ｍｌ－１。结论：两种剂型的药物动力学参数之间差异均无显著性（Ｐ＞０．０５），胶囊剂的相对生物利用度为９９．８８％。     

盐酸林可霉素口服液在人体内药动学和生物利用度

８名健康受试者一次口服盐酸林可霉素的口服液和片剂两种剂型后，用高效液相－电化学（ＨＰＬＣ－ＥＤ）法测定盐酸林可霉素的血药浓度，其血药浓度符合一室模型。结果盐酸林可霉素口服液和片剂主要药动学参数分别为：Ｃ_(ｍａｘ)：５．０±０．５ｍｇ／Ｌ和４．３±０．６ｍｇ／Ｌ；Ｔｍａｘ：２．１６±０．２１ｈ和２．３±０．６ｈ；ＡＵＣ：３７±７（ｍｇ·ｈ）／Ｌ和３６±７（ｍｇ·ｈ）／Ｌ。盐酸林可霉素口服液对片剂的相对生物利用度为１０４±５％，可认为口服液与片剂生物等效。     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

Self-stimulation and amphetamine: Tolerance to d and l isomers and cross tolerance to cocaine and methylphenidate

The effects of the d and l isomers of amphetamine on self-stimulation responding were tested following acute and chronic administration. Tolerance and post-drug depression of responding occurred in tests with both isomers, indicating no role for p-hydroxynorephedrine (PHN) which is one of the metabolites of d-amphetamine. In the second experiment, d-amphetamine, methylphenidate and cocaine all produced quantitatively and qualitatively similar effects on self-stimulation responding following acute administration. Following chronic administration of d-amphetamine, animals showed tolerance to all three drugs, indicating cross-tolerance among them. These data are consistent with an hypothesis that tolerance and post-drug depression following chronic amphetamine treatment are the result of decreases in postsynaptic receptor sensitivity, which would lead to a decreased effectiveness of all three drugs, regardless of their pre-synaptic mechanisms.     

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Rationale  Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans. Objectives  The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats. Materials and methods  In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers. Results  Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats. Conclusions  The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.