AAPS PharmSci最新文献_第2页

Electronic and resonance effects on the lonization of structural analogues of efavirenz 依非韦伦结构类似物离子化的电子和共振效应

AAPS PharmSci Pub Date : 2008-01-01 DOI: 10.1208/ps030428

S. Rabel, S. Sun, M. Maurin, Mona Patel

引用次数: 17

Is antisense an appropriate nomenclature or design for oligodeoxynucleotides aimed at the inhibition of HIV-1 replication? 反义是抑制HIV-1复制的寡脱氧核苷酸的恰当命名或设计吗?

AAPS PharmSci Pub Date : 2008-01-01 DOI: 10.1208/ps040207

C. Lavigne, J. Yelle, G. Sauvé, A. Thierry

{"title":"Is antisense an appropriate nomenclature or design for oligodeoxynucleotides aimed at the inhibition of HIV-1 replication?","authors":"C. Lavigne, J. Yelle, G. Sauvé, A. Thierry","doi":"10.1208/ps040207","DOIUrl":"https://doi.org/10.1208/ps040207","url":null,"abstract":"We have evaluated the specificity and the variation in activity against human immunodeficiency virus (HIV) infection of antisense oligodeoxynucleotides (ODNs) with regard to factors such as dose-response range, number and choice of experimental controls, backbone modifications of the ODNs, type of cell infection, length of assays, and delivery approach. The highest level of inhibition was achieved in our long-term assay with MOLT-3 cells acutely infected with HIV-1 (IIIB0 and treated with free phosphorothioate-modified ODNs (PS-ODNs). The highest level of specificity was observed in our short-term assay with MOLT-3 cells acutely infected with HIV-1 (IIIB) and treated with free PS-ODNs. the highest potency (IC50 level) was observed in our short-term chronic-infection model with (DLS)-delivered ODNs in which the DLS delivery improved the ODN activity up to 106 times compared to the activity of free ODNs. Thus, the near blocking of HIV replication obtained when using PS-ODNs appears because of the addition of extracellular and/or membranar effects. The higher efficacy of PS-ODNs compared to unmodified ODNs, when both are delivered with the DLS system, was demonstrated solely in our short-term assay with MOLT-3 cells. Important variations in the level of sequence specificity were observed and depended on the type of control used and the type of cell assay employed. It seems that all 3 groups of control-tested, random, sense sequence, and non-antisense T30177 ODNs might have distinct activity and, consequently, different modes of action in inhibiting HIV replication. Our data buttress the notion that the contribution of the sequence-specific mediated mode of action is minor compared to the other mechanisms involved in ODN antiviral activity.","PeriodicalId":6918,"journal":{"name":"AAPS PharmSci","volume":"37 1","pages":"34-44"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76405220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Skeletal effects of parathyroid hormone (1–34) in ovariectomized rats with or without concurrent administration of salmon calcitonin 切除卵巢大鼠同时服用或不同时服用鲑鱼降钙素时甲状旁腺激素(1-34)对骨骼的影响

AAPS PharmSci Pub Date : 2008-01-01 DOI: 10.1208/ps030427

B. Dani, P. Deluca

{"title":"Skeletal effects of parathyroid hormone (1–34) in ovariectomized rats with or without concurrent administration of salmon calcitonin","authors":"B. Dani, P. Deluca","doi":"10.1208/ps030427","DOIUrl":"https://doi.org/10.1208/ps030427","url":null,"abstract":"This study evaluated the effect of parathyroid hormone (PTH) infusion alone or in combination with salmon calcitonin (sCT) in ovariectomized (OVX) rats and compared it with daily PTH injections alone or in combination with sCT infusion. Female Sprague-Dawley rats were divided randomly into 6 groups and were either bilaterally ovariectomized or underwent a sham operation; they were then treated for 4 weeks, beginning the day after surgery. Each group of OVX rats received either PTH infusion (group 1), PTH+sCT infusion (group 2), sCT infusion+daily PTH injection (group 3), or daily PTH injection (group 4). One group each of OVX (group 5) and sham-operated rats (group 6) received daily injections of vehicle alone. PTH was injected at 80 μg/kg/day and infused at 40 μg/kg/day, whereas sCT was infused at 10 μg/kg/day. The animals were sacrificed 28 days after treatment, and cancellous bone volume was measured in the tibial metaphysis. Similar to daily PTH injections, continuous infusion of PTH alone increased cancellous bone volume significantly over that seen in vehicle-treated OVX and sham-operated rats. Although cancellous bone volume after continuous infusion of PTH+sCT was also significantly higher than that seen in vehicle-treated OVX and sham-operated rats, the increase was significantly lower than with the other 3 nonvehicle treatments. The increase in cancellous bone volume after administration of sCT infusion along with daily PTH injections was not different from that with daily PTH injections alone. Thus, at the doses tested, the beneficial effects of PTH injection were not apparently improved by PTH infusion or by combination with sCT.","PeriodicalId":6918,"journal":{"name":"AAPS PharmSci","volume":"90 1","pages":"19-25"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84079133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 19

Encapsulation of water-insoluble drug by a cross-linking technique: effect of process and formulation variables on encapsulation efficiency, particle size, and in vitro dissolution rate. 交联技术对水不溶性药物的包封:工艺和配方变量对包封效率、粒径和体外溶出率的影响。

AAPS PharmSci Pub Date : 2004-03-22 DOI: 10.1208/ps060112

Pralhad T Tayade, Rajendrakumar D Kale

{"title":"Encapsulation of water-insoluble drug by a cross-linking technique: effect of process and formulation variables on encapsulation efficiency, particle size, and in vitro dissolution rate.","authors":"Pralhad T Tayade, Rajendrakumar D Kale","doi":"10.1208/ps060112","DOIUrl":"https://doi.org/10.1208/ps060112","url":null,"abstract":"Ibuprofen-gelatin micropellets were prepared by the cross-linking technique using formaldehyde. Spherical micropellets having an entrapment efficiency of 65% to 85% were obtained. The effect of core to coat ratio, speed of agitation, temperature, and volume of oil phase was studied with respect to entrapment efficiency, micropellet size, and surface characteristics. Fourier transform infrared spectroscopy and differential scanning calorimetric analysis confirmed the absence of any drug-polymer interaction. X-ray diffraction patterns showed that there is a decrease in crystallinity of the drug. The micromeritic properties of micropellets were found to be slightly changed by changing various processing parameters to give micropellets of good flow property. The in vitro release profile could be altered significantly by changing various processing parameters to give a controlled release of drug from the micropellets. The stability studies of the drug-loaded micropellets showed that the drug was stable at storage conditions of room temperature, 37 degrees C, 25 degrees/60% relative humidity (RH) and 45 degrees/60% RH, for 12 weeks.","PeriodicalId":6918,"journal":{"name":"AAPS PharmSci","volume":"6 1","pages":"E12"},"PeriodicalIF":0.0,"publicationDate":"2004-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1208/ps060112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24566596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 58

Assuring quality and performance of sustained and controlled release parenterals: EUFEPS workshop report. 确保持续控释制剂的质量和性能:EUFEPS车间报告。

AAPS PharmSci Pub Date : 2004-03-22 DOI: 10.1208/ps060111

Diane J Burgess, Daan J A Crommelin, Ajaz S Hussain, Mei-Ling Chen

{"title":"Assuring quality and performance of sustained and controlled release parenterals: EUFEPS workshop report.","authors":"Diane J Burgess, Daan J A Crommelin, Ajaz S Hussain, Mei-Ling Chen","doi":"10.1208/ps060111","DOIUrl":"https://doi.org/10.1208/ps060111","url":null,"abstract":"This is a summary report of the workshop, organized by the European Federation of Pharmaceutical Scientists in association with the American Association of Pharmaceutical Scientists, the European Agency for the Evaluation of Medicinal Products, the European Pharmacopoeia, the US Food and Drug Administration and the United States Pharmacopoeia, on \"Assuring Quality and Performance of Sustained and Controlled Release Parenterals\" held in Basel, Switzerland, February 2003. Experts from the pharmaceutical industry, regulatory authorities and academia participated in this workshop to review, discuss and debate formulation, processing and manufacture of sustained and controlled release parenterals, and identify critical process parameters and their control. This workshop was a follow-up workshop to a previous workshop on Assuring Quality and Performance of Sustained and Controlled Release Parenterals that was held in Washington, DC in April 2001. This report reflects the outcome of the Basel 2003 meeting and the advances in the field since the Washington, DC meeting in 2001. As necessary, the reader is referred to the report on the 2001 meeting. Areas were identified at the 2003 Basel meeting where research is needed in order to understand the performance of these drug delivery systems and to assist in the development of appropriate testing procedures. Recommendations were made for future workshops and meetings.","PeriodicalId":6918,"journal":{"name":"AAPS PharmSci","volume":"6 1","pages":"E11"},"PeriodicalIF":0.0,"publicationDate":"2004-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1208/ps060111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24566595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 54

Assessment of fertility in male rats after extended chemical castration with a GnRH antagonist. 用GnRH拮抗剂评估雄性大鼠长期化学阉割后的生育能力。

AAPS PharmSci Pub Date : 2004-03-11 DOI: 10.1208/ps060110

Susan S D'Souza, Francesca Selmin, Santos B Murty, Wei Qiu, B C Thanoo, Patrick P DeLuca

{"title":"Assessment of fertility in male rats after extended chemical castration with a GnRH antagonist.","authors":"Susan S D'Souza, Francesca Selmin, Santos B Murty, Wei Qiu, B C Thanoo, Patrick P DeLuca","doi":"10.1208/ps060110","DOIUrl":"https://doi.org/10.1208/ps060110","url":null,"abstract":"The purpose of this study was to assess whether male rats whose testosterone levels were suppressed to castration levels (<0.5 ng/mL) for a 1-year period by the sustained delivery of orntide acetate, a GnRH antagonist, would return to fertility (ie, produce offspring) after serum testosterone returned to control levels. Male rats comprising a treatment group (orntide microspheres, dose = 27 mg/kg/y), a vehicle control group, and a control group of proven male breeders were used. For the treatment and vehicle control groups, serum orntide and testosterone levels were monitored at periodic intervals for 14 months from the initiation of treatment. After serum testosterone levels returned to vehicle control levels and orntide serum levels were no longer discernible for the treated group, each of the animals was housed with 2 drug-naive, female, proven breeders. All the breeder females produced offspring with the exception of 1 female housed with a male rat from the treatment group and the 2 females housed with a single male rat from the vehicle control group. The mean size and weight of the litters from each group were not statistically different. Further, fertility of the offspring from each group was assessed. The male and female offspring studied were all shown to be fertile. The results suggest that lack of fertility due to testosterone suppression in male rats is reversible after cessation of treatment with the GnRH analog, orntide.","PeriodicalId":6918,"journal":{"name":"AAPS PharmSci","volume":"6 1","pages":"E10"},"PeriodicalIF":0.0,"publicationDate":"2004-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1208/ps060110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24566594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 26

Development and characterization of a recombinant Madin-Darby canine kidney cell line that expresses rat multidrug resistance-associated protein 1 (rMRP1). 表达大鼠多药耐药相关蛋白1 (rMRP1)的重组Madin-Darby犬肾细胞系的建立和鉴定

AAPS PharmSci Pub Date : 2004-03-09 DOI: 10.1208/ps060108

Ziping Yang, Micha Horn, Joanne Wang, Danny D Shen, Rodney J Y Ho

{"title":"Development and characterization of a recombinant Madin-Darby canine kidney cell line that expresses rat multidrug resistance-associated protein 1 (rMRP1).","authors":"Ziping Yang, Micha Horn, Joanne Wang, Danny D Shen, Rodney J Y Ho","doi":"10.1208/ps060108","DOIUrl":"https://doi.org/10.1208/ps060108","url":null,"abstract":"Multidrug resistance-associated protein 1 (MRP1) is one of the major proteins shown to mediate efflux transport of a broad range of antitumor drugs, glucuronide conjugates, and glutathione, in addition to endogenous substrates. Significant differences in substrate selectivity were reported for murine and human MRP1. As preclinical drug disposition and pharmacokinetics studies are often conducted in rats, we have recently cloned the rat MRP1 (rMRP1) and demonstrated that rMRP1 expressed in transfected cells effluxes calcein, a commonly used fluorescence substrate for human MRP1. To further characterize the rat ortholog of MRP1, we isolated a cell line stably expressing recombinant rMRP1. These cells were tested for their ability to transport calcein and a range of chemotherapeutic drugs. Our results showed that cells expressing rMRP1 consistently efflux calcein at a rate 5-fold greater than control cells. The rMRP1 transfected cells, like their human ortholog, can confer drug resistance to vinca alkaloid (vinblastine and vincristine) and anthracycline drugs (daunorubcin and doxorubicin), and the resistance conferred by the MRP1 can be partially abolished by the MRP-specific inhibitors. The transepithelial permeability due to rMRP1 expression in differentiated Madin-Darby canine kidney cells (MDCK) cells was also investigated. The MRP1 transport activity is directional, as demonstrated by directional vinblastine transport. Collectively, our results demonstrate that the cellular expression of rMRP1, like its human ortholog, could confer resistance to anticancer drugs.","PeriodicalId":6918,"journal":{"name":"AAPS PharmSci","volume":"6 1","pages":"E8"},"PeriodicalIF":0.0,"publicationDate":"2004-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1208/ps060108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24566592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Pharmacokinetic model of target-mediated disposition of thrombopoietin. 靶介导的血小板生成素处置的药代动力学模型。

AAPS PharmSci Pub Date : 2004-03-09 DOI: 10.1208/ps060109

Feng Jin, Wojciech Krzyzanski

引用次数: 37

Beta-cyclodextrin complexes of celecoxib: molecular-modeling, characterization, and dissolution studies. 塞来昔布的β-环糊精复合物：分子建模、表征和溶出度研究。

AAPS PharmSci Pub Date : 2004-03-05 DOI: 10.1208/ps060107

M Narender Reddy, Tasneem Rehana, S Ramakrishna, K P R Chowdhary, P V Diwan

{"title":"Beta-cyclodextrin complexes of celecoxib: molecular-modeling, characterization, and dissolution studies.","authors":"M Narender Reddy, Tasneem Rehana, S Ramakrishna, K P R Chowdhary, P V Diwan","doi":"10.1208/ps060107","DOIUrl":"10.1208/ps060107","url":null,"abstract":"Celecoxib, a specific inhibitor of cycloxygenase-2 (COX-2) is a poorly water-soluble nonsteroidal anti-inflammatory drug with relatively low bioavailability. The effect of beta-cyclodextrin on the aqueous solubility and dissolution rate of celecoxib was investigated. The possibility of molecular arrangement of inclusion complexes of celecoxib and beta-cyclodextrin were studied using molecular modeling and structural designing. The results offer a better correlation in terms of orientation of celecoxib inside the cyclodextrin cavity. Phase-solubility profile indicated that the solubility of celecoxib was significantly increased in the presence of beta-cyclodextrin and was classified as A(L)-type, indicating the 1:1 stoichiometric inclusion complexes. Solid complexes prepared by freeze drying, evaporation, and kneading methods were characterized using differential scanning calorimetry, powder x-ray diffractometry, and scanning electron microscopy. In vitro studies showed that the solubility and dissolution rate of celecoxib were significantly improved by complexation with beta-cyclodextrin with respect to the drug alone. In contrast, freeze-dried complexes showed higher dissolution rate than the other complexes.","PeriodicalId":6918,"journal":{"name":"AAPS PharmSci","volume":"6 1","pages":"E7"},"PeriodicalIF":0.0,"publicationDate":"2004-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1208/ps060107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24566591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 120

Physiologically based pharmacokinetics in drug development and regulatory science: a workshop report (Georgetown University, Washington, DC, May 29-30, 2002). 药物开发和监管科学中基于生理学的药代动力学:研讨会报告(乔治城大学，华盛顿特区，2002年5月29-30日)。

AAPS PharmSci Pub Date : 2004-02-09 DOI: 10.1208/ps060106

Malcolm Rowland, Luc Balant, Carl Peck

{"title":"Physiologically based pharmacokinetics in drug development and regulatory science: a workshop report (Georgetown University, Washington, DC, May 29-30, 2002).","authors":"Malcolm Rowland, Luc Balant, Carl Peck","doi":"10.1208/ps060106","DOIUrl":"https://doi.org/10.1208/ps060106","url":null,"abstract":"A 2-day workshop on \"Physiologically Based Pharmacokinetics (PBPK) in Drug Development and Regulatory Science\" came to a successful conclusion on May 30, 2002, in Washington, DC. More than 120 international participants from the environmental and predominantly pharmaceutical industries, Food and Drug Administration (FDA), and universities attended this workshop, organized by the Center for Drug Development Science, Georgetown University, Washington, DC. The first of its kind specifically devoted to the subject, this intensive workshop, comprising 7 plenary presentations and 10 breakout sessions addressed 2 major objectives: (1) to \"define demonstrated and potential contributions of PBPK in drug development and regulatory science,\" and (2) to \"assess current PBPK methodologies with the identification of their limitations and outstanding issues.\" This report summarizes the presentations and recommendations that emerged from the workshop, while providing key references, software, and PBPK data sources in the appendices. The first day was initially devoted to presentations setting the stage and providing demonstrated applications to date. This was followed by breakout sessions that considered further opportunities and limitations, and which extended into Day 2 to deal with developments in methodologies and tools. Although the primary emphasis was on pharmacokinetics, consideration was also given to its integration specifically with mechanism-based pharmacodynamics.","PeriodicalId":6918,"journal":{"name":"AAPS PharmSci","volume":"6 1","pages":"E6"},"PeriodicalIF":0.0,"publicationDate":"2004-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1208/ps060106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24566590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 118