• Title/Summary/Keyword: new drugs

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Analysis of Interval-censored Survival Data from Crossover Trials with Proportional Hazards Model (교차계획 구간절단 생존자료의 비례위험모형을 이용한 분석)

  • Kim, Eun-Young;Song, Hae-Hiang
    • The Korean Journal of Applied Statistics
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    • v.20 no.1
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    • pp.39-52
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    • 2007
  • Crossover trials of new drugs in the treatment of angina pectoris, which frequently use treadmill exercise test for the assessment of its efficacy, produce censored survival times. In this paper we consider analysis approaches for censored survival times from crossover trials. Previously, a stratified Cox model for paired observation and nonparametric methods have been presented as possible analysis methods. On the other hand, the differences of two survival times would produce interval-censored survival times and we propose a Cox model for interval-censored data as n alternative analysis method. Example data is analyzed in order to compare these different methods.

Pre-clinical QT Risk Assessment in Pharmaceutical Companies - Issues of Current QT Risk Assessment -

  • Takasuna, Kiyoshi; Katsuyoshi, Chiba;Manabe, Sunao
    • Biomolecules & Therapeutics
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    • v.17 no.1
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    • pp.1-11
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    • 2009
  • Since the Committee for Proprietary Medicinal Products (CPMP) of the European Union issued in 1997 a "points to consider" document for the assessment of the potential for QT interval prolongation by non-cardiovascular agents to predict drug-induced torsades de pointes (TdP), the QT liability has become the critical safety issue in the development of pharmaceuticals. As TdP is usually linked to delayed cardiac repolarization, international guideline (ICH S7B) has advocated the standard repolarization assays such as in vitro IKr (hERG current) and in vivo QT interval, or in vitro APD (as a follow up) as the best biomarkers for predicting the TdP risk. However, the recent increasing evidence suggests that the currently used above biomarkers and/or assays are not fully predictive for TdP, but also does not address potential new druginduced TdP due to the selective disruption of hERG protein trafficking to the cell membrane or VT and/or VF with QT shortening. There is, therefore, an urgent need for other surrogate markers or assays that can predict the proarrhythmic potential of drug candidate. In this review, we provide an ideal pre-clinical strategy to predict the potentials of QT liability and lethal arrhythmia of the drug candidates with recent issues in this field in mind, not at the expense of discarding therapeutically innovative drugs.

Suppressive Actions of Astragali Radix (AR) Ethanol Extract and Isolated Astragaloside I on HCl/ethanol-Induced Gastric Lesions

  • Jeong, Jeong-Suk;Lee, Je-Hyuk;Lee, Sang-Hyup;Kang, Sam-Sik;Jeong, Choon-Sik
    • Biomolecules & Therapeutics
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    • v.17 no.1
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    • pp.62-69
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    • 2009
  • Roots of Astragalus membranaceus (A. membranaceus) (Astragali Radix, AR) has been used as a herbal medicine for gastrointestinal disorders in China, Korea, Japan, and other Asia countries. In this study we investigated the effects of the AR 70% ethanol extract and compounds isolated from AR on gastritis in rats and growth of human gastric cancer cells. AR 70% ethanol extract showed the potent acid-neutralizing capacities and partly cytotoxicity of Helicobacter pylori and human AGS gastric cancers cell. Astragaloside I and daucosterol, which were isolated from AR, significantly inhibited HCl/ethanol-induced gastric lesions. In addition, daucosterol increased the mucus content to almost the same as the positive control. The results of this study suggest that astragaloside I and daucosterol may be good candidates for the development of new drugs or neutraceuticals which can be used for the treatment or prevention of gastritis.

Gefitinib Inhibits the Growth of Toxoplasma gondii in HeLa Cells

  • Yang, Zhaoshou;Ahn, Hye-Jin;Nam, Ho-Woo
    • Parasites, Hosts and Diseases
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    • v.52 no.4
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    • pp.439-441
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    • 2014
  • Toxoplasma gondii is the causative agent of toxoplasmosis with symptoms of congenital neurological and ocular diseases and acquired lymphadenitis, retinochoroiditis, and meningoencephalitis. Small molecules which block the activity of protein kinases were tested in in vitro culture of T. gondii to find new therapeutic drugs of safer and more effective than the combined administration of pyrimethamine and sulfadoxine that sometimes provoke lethal Stevens-Johnson syndrome. Among them, Gefitinib and Crizotinib inhibited intracellular growth of T. gondii in HeLa cells by counting the number of T. gondii per parasitophorous vacuolar membrane whereas Sunitinib did not. Gefitinib inhibited the growth of T. gondii in a dose-dependent manner over $5{\mu}M$ up to the tolerable concentration of HeLa cells and halted the division of the parasite immediately from the time point of treatment. Gefitinib inhibition suggests that tyrosine kinases of EGFR family or other homologous kinases of the parasite itself may be the target to cause the block of T. gondii growth.

Hepatitis C Viral Infection in Children: Updated Review

  • El-Guindi, Mohamed A.
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.19 no.2
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    • pp.83-95
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    • 2016
  • Hepatitis C virus (HCV) infection is a major medical challenge affecting around 200 million people worldwide. The main site of HCV replication is the hepatocytes of the liver. HCV is a positive enveloped RNA virus from the flaviviridae family. Six major HCV genotypes are implicated in the human infection. In developed countries the children are infected mainly through vertical transmission during deliveries, while in developing countries it is still due to horizontal transmission from adults. Minimal nonspecific and brief symptoms are initially found in approximately 15% of children. Acute and chronic HCV infection is diagnosed through the recognition of HCV RNA. The main objective for treatment of chronic HCV is to convert detected HCV viremia to below the detection limit. Children with chronic HCV infection are usually asymptomatic and rarely develop severe liver damage. Therefore, the benefits from current therapies, pegylated-Interferon plus ribavirin, must be weighed against their adverse effects. This combined treatment offers a 50-90% chance of clearing HCV infection according to several studies and on different HCV genotype. Recent direct acting antiviral (DAA) drugs which are well established for adults have not yet been approved for children and young adults below 18 years. The most important field for the prevention of HCV infection in children would be the prevention of perinatal and parenteral transmission. There are areas of focus for new lines of research in pediatric HCV-related disease that can be addressed in the near future.

Pulmonary Paragonimiasis Misdiagnosed with Pulmonary Tuberculosis (객혈과 공동 폐병변으로 폐결핵으로 오인된 폐흡충증 1예)

  • Park, Su Eun;Song, Bokyung;Hwang, Jae-Yeon
    • Pediatric Infection and Vaccine
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    • v.24 no.3
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    • pp.178-182
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    • 2017
  • Paragonimiasis was one of the most common causes of cavitary lung lesions until the 1960s, but now it has become a very rare disease in Korea. A 16-year-old boy presented with hemoptysis and several days of cough. His plain chest radiograph showed nodular opacity with a cavity in the left upper lung region. Although his symptoms disappeared after taking antituberculous drugs, his plain chest radiograph and computed tomography images after completion of therapy showed a new nodule with a cavity in the left lung field. Through video-assisted thoracoscopic wedge resection, Paragonimus eggs were found in the lung tissues.

Studies on the Identification Test of Herbal Medicines and its Preparations (한약엑스제의 확인시험법에 관한 연구)

  • Kim, Hye-Jin;Suh, Yong-Taek;Lee, Jong-Pill;Cho, Jung-Hee;Jang, Young-Pyo
    • Korean Journal of Pharmacognosy
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    • v.40 no.2
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    • pp.155-160
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    • 2009
  • The reference herbal extracts and their identification methods by Korean Pharmacopoeia IX were established based on the organic solvent extracts to detect their marker compounds. However, most of herbal medicine decoctions in the market are prepared with water as extracting solvent. As the reference herbal extracts and their identification methods are not appropriate for the practical test, new preparation of alternative reference herbal extracts and their identification test methods are essential for the correction of test methods and identification of herbal drugs. Three novel identification test methods were developed for Evodiae Fructus, Cimicifugae Rhizoma and Aurantii Fructus Immaturus. Total 10 reference herbal extracts and their identification methods were optimized for Ephedrae Herba, Schisandrae Fructus, Curcuma longae Rhizoma, Citri Unshius Pericarpium, Puerariae Radix, Corni Fructus, and Cinnamomi Cortex.

Knowledge-based Herbal Database for the Treatment of Atopic Dermatitis (아토피피부염 치료를 위한 지식기반의 생약 데이터베이스)

  • Shin, Jee-Young;Bae, Hyun-Su;Hong, Mu-Chang;Shin, Min-Kyu;Kim, Yang-Seok
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.6
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    • pp.1129-1133
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    • 2010
  • The treatment of Atopic dermatitis and its untapped herbal elements are recognized as possible solutions to incurable diseases stemming from overdosage of chemical drugs. Synthesizing clinical results from the Oriental medicine with scientific results from the field of Molecular biology is in the mainstream. The main goal of this research is, by objectifying the methodology of abstracting information into a compendium, to establish knowledge-based database on natural materials mingling every single related information from both Oriental and Western medicine. The constructed system, ATODERM, is the first database system about the medical herb for the treatment of Atopic Dermatitis which bearing the integrated information on Oriental medicine and Western medicine. The construction of this database renders new ways of treatment and prescriptions for researchers in the field of the Oriental medicine. Using the database that has been intensively accumulated, the possibility of creating the plausible cure for the disease can be anticipated.

High-performance liquid chromatographic assay and oral pharmacokinetics of new anti-HIV uracil derivatives, KR-V analogues, in rats

  • Lee, Youngmi;Heeok Shim;Seoungryong Yu;Hochul Shin;Moonkoo Chung;Jungkoo Roh
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.11a
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    • pp.123-123
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    • 1998
  • A number of uracil derivatives have been developed as anti-AIDS drugs having a mechanism of inhibiting cellular reverse transcriptase. A simple and rapid assay technique for recently synthesized KR-V analogues was developed using a high-performance liquid chromatography, and oral pharmacokinetics was examined for assessing their oral bioavailabilites. Plasma samples were analyzed by reversed-phase HPLC using an ODS column with an ultraviolet detection system. All the analogues were eluted within 12 min and the LOQ was 15-30 ng/$m\ell$. The extraction recoveries were higher than 85%, except KR-V1039, 1068 and 1720 having ester group. This chromatic method was well applied to the kinetic studies for KR-V analogues. Among 16 analogues tested in the present work, the 6 compounds including KR-V1123, 1122, 1784, 1783, 1736 and 1700 were found to be bioavailable for oral administration to rats.

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F1064m: New Inhibitor of Cholesteryl Ester Transfer Protein (CETP), Isolated from Gliocladium virens F1064

  • Kwon, Byoung-Mog;Cho, Joung-Suk;Jeong, Tae-Sook;Kim, Sung-Uk;Son, Kwang-Hee;Kim, Young-Kook;Nam, Ji-Youn;Han, Kyu-Hoon;Bok, Song-Hae
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1995.04a
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    • pp.65-65
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    • 1995
  • Cholesteryl Ester Transfer Protein(CETP), a hydrophobic glycoprotein with molecular mass 74KDa, is a lipid transfer protein found in plasma which mediates the transfer of cholesterol ester and triglyceride between high-density lipoprotein (HDL) and other lipoproteins, therefore, it might influence HDL levels. The lipoprotein profile associated with human CETP deficiency (that are two Japanese families, high HDL and low LDL) has low atherogenic potential, raising the possibility that CETP inhibitors can be used as antiatherosclerotic drugs.

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