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排序方式: 共有219条查询结果,搜索用时 13 毫秒
1.
Krondahl Eva Orzechowski Achim Ekström Gunilla Lennernäs Hans 《Pharmaceutical research》1997,14(12):1780-1785
Purpose. To study intestinal transport and metabolism of three new -selective tetrapeptide enkephalin analogues, LEF537, LEF553 and TAPP These peptides are stabilized against enzymatic hydrolysis by having a D-aminoacid in position 2 and a blocked COOH-terminal.
Methods. We used a single-pass perfusion technique to study the transport of the peptides in rat jejunum. To reduce luminal and/or brush-border metabolism during the perfusion we used protease inhibitors (Pefabloc® SC, bestatin and thiorphan). The rate of metabolism was studied by incubations in rat jejunal homogenate, rat jejunal fluid and human gastric and jejunal fluid with and without these inhibitors.
Results. The jejunal permeabilities (Peff) of the peptides were 0.43–0.78 10–4 cm/s without inhibitors and 0.09–0.45 10–4 cm/s in presence of the inhibitors. All three peptides were rather rapidly degraded by enzymes in rat jejunal homogenate with half-lives of between 11.9 ± 0.5 and 31.7 ± 1.5 min. The addition of inhibitors to the homogenate prolonged the half-lives substantially for LEF553 (167 ± 35 min) and TAPP (147 ± 2 min), but only slightly for LEF537 (16.4 ± 0.5 min). LEF553 and TAPP were both hydrolyzed in rat and human jejunal fluid, while LEF537 was metabolized less in these fluids. When LEF553 and TAPP were incubated with intestinal fluid in the presence of inhibitors, metabolism was almost completely inhibited. There was no metabolism for any of the peptides in human gastric juice.
Conclusions. The replacement of the terminal free carboxylic group with an amide group did not increase the stability of the peptides in jejunal tissue enough to allow successful oral drug delivery. 相似文献
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Antonios Douros Elisabeth Bronder Frank Andersohn Andreas Klimpel Michael Thomae Hans-Dieter Orzechowski Reinhold Kreutz Edeltraut Garbe 《European journal of clinical pharmacology》2014,70(4):453-459
Purpose
The hepatotoxic potential of the analgesic flupirtine has attracted increased attention over the past years. Recently, risk minimisation measures such as maximum treatment duration of 2 weeks have been requested by the European Medicines Agency (EMA). This study was conducted to further elucidate the clinical pattern of flupirtine-induced liver injury (FILI).Methods
Seven FILI patients were ascertained in all Berlin hospitals in the Berlin Case–control Surveillance Study (FAKOS) between 2002 and 2011. Furthermore, we reviewed the severe cases of flupirtine-associated hepatotoxicity included in the adverse drug reaction database of the Federal Institute for Drugs and Medical Devices (BfArM) in Germany from between 1991 and 2012.Results
All seven FILI patients of FAKOS were hospitalised. Six of them were female, mean age was 55 years, and the most common symptoms were fatigue and jaundice. Three patients developed acute liver failure (ALF). Discontinuation of flupirtine invariably led to clinical and laboratory improvement. Review of the BfArM cases (n?=?248) showed female sex predominance and high prevalence of jaundice and ALF. Time to onset of symptoms was less than 2 weeks in 9 % of the patients with respective data.Conclusions
Our results corroborate previous findings on FILI’s clinical pattern and on its potentially severe course. Although the hepatotoxic risk might be higher after the first 2 weeks of treatment, earlier onset of severe FILI cannot be ruled out. Postauthorisation safety studies are needed to evaluate EMA’s risk minimisation measures and to quantify flupirtine’s risk according to its duration of use. 相似文献5.
Piotr Orzechowski MD Ryszard Piotrowicz MD PhD Wojciech Zaręba MD PhD Renata Główczyńska MD PhD Dominika Szalewska MD PhD Sławomir Pluta MD PhD Robert Irzmański MD PhD Zbigniew Kalarus MD PhD Maciej Banach MD PhD Grzegorz Opolski MD PhD Michael J. Pencina PhD Ilona Kowalik PhD Ewa Piotrowicz MD PhD FESC 《Annals of noninvasive electrocardiology》2021,26(6):e12887
6.
Rossana Patricia Basso Vanice Rodrigues Poester Jssica Louise Benelli David A. Stevens Melissa Orzechowski Xavier 《Emerging infectious diseases》2022,28(3):721
We evaluated disseminated histoplasmosis (DH) in HIV patients over 10 years in southern Brazil. The incidence was 12 cases/1,000 hospitalizations (2010–2019); the mortality rate was 35%. Tuberculosis frequently obscured the diagnosis of DH. We emphasize the need in our region to suspect and investigate DH using more sensitive methods. 相似文献
7.
Werner Faust Konrad Lang Lehnartz Druckrey A. Fröhlich Langendorff Demuth Hartmann Hinsberg Orzechowski Mühlbock A. Juhász-Schäffer Reiss 《Journal of cancer research and clinical oncology》1936,43(2-3):74-80
Ohne Zusammenfassung 相似文献
8.
Gerhard Orzechowski Wolff Harzer Regelsberger A. Loeb Demme Gänssle Stengel 《Journal of molecular medicine (Berlin, Germany)》1930,9(42):1986-1990
Ohne Zusammenfassung 相似文献
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Küster Hans W. Schmidt E. Jacob W. Fischer Haagen A. Schmitz Merten Kloiber Annelise Schlüter Ostertag H. Nachtsheim Kürten Hans W. Schmidt Pohlandt Voss Breitländer Orzechowski Druckrey Krah Th. Naegeli Franz Sørensen Werthemann 《Journal of cancer research and clinical oncology》1942,53(3-4):188-199
Ohne Zusammenfassung 相似文献