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  1. Book ; Thesis: Wirkung einer einwöchigen Behandlung mit Ticlopidin und Acetylsalicylsäure auf die Thrombogene Membrantransformation von Humanthrombozyten

    Strotmann, Rainer

    Vergleich diabetischer und stoffwechselgesunder Probanden

    1997  

    Author's details vorgelegt von Rainer Strotmann
    Language German
    Size 75 Bl. : graph. Darst.
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Düsseldorf, Univ., Diss., 1997
    HBZ-ID HT009522076
    Database Catalogue ZB MED Medicine, Health

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    99 E 1204 order for loan Magazin

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  2. Article ; Online: Population pharmacokinetic analysis of tepotinib, an oral MET kinase inhibitor, including data from the VISION study.

    Xiong, Wenyuan / Papasouliotis, Orestis / Jonsson, E Niclas / Strotmann, Rainer / Girard, Pascal

    Cancer chemotherapy and pharmacology

    2022  Volume 89, Issue 5, Page(s) 655–669

    Abstract: Purpose: Tepotinib is a highly selective, potent, mesenchymal-epithelial transition factor (MET) inhibitor, approved for the treatment of non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping. Objectives of this population pharmacokinetic ( ... ...

    Abstract Purpose: Tepotinib is a highly selective, potent, mesenchymal-epithelial transition factor (MET) inhibitor, approved for the treatment of non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping. Objectives of this population pharmacokinetic (PK) analysis were to evaluate the dose-exposure relationship of tepotinib and its major circulating metabolite, MSC2571109A, and to identify the intrinsic/extrinsic factors that are predictive of PK variability.
    Methods: Data were included from 12 studies in patients with cancer and in healthy participants. A sequential modeling approach was used to analyze the parent and metabolite data, including covariate analyses. Potential associations between observed covariates and PK parameters were illustrated using bootstrap analysis-based forest plots.
    Results: A two-compartment model with sequential zero- and first-order absorption, and a first-order elimination from the central compartment, best described the plasma PK of tepotinib in humans across the dose range of 30-1400 mg. The bioavailability of tepotinib was shown to be dose dependent, although bioavailability decreased primarily at doses above the therapeutic dose of 500 mg. The intrinsic factors of race, age, sex, body weight, mild/moderate hepatic impairment and mild/moderate renal impairment, along with the extrinsic factors of opioid analgesic and gefitinib intake, had no relevant effect on tepotinib PK. Tepotinib has a long effective half-life of ~ 32 h.
    Conclusions: Tepotinib shows dose proportionality up to at least the therapeutic dose, and time-independent clearance with a profile appropriate for once-daily dosing. None of the covariates identified had a clinically meaningful effect on tepotinib exposure or required dose adjustments.
    MeSH term(s) Antineoplastic Agents/therapeutic use ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Humans ; Lung Neoplasms/drug therapy ; Piperidines ; Protein Kinase Inhibitors/pharmacokinetics ; Proto-Oncogene Proteins c-met ; Pyridazines ; Pyrimidines
    Chemical Substances Antineoplastic Agents ; Piperidines ; Protein Kinase Inhibitors ; Pyridazines ; Pyrimidines ; tepotinib (1IJV77EI07) ; Proto-Oncogene Proteins c-met (EC 2.7.10.1)
    Language English
    Publishing date 2022-04-06
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 6820-2
    ISSN 1432-0843 ; 0344-5704 ; 0943-9404
    ISSN (online) 1432-0843
    ISSN 0344-5704 ; 0943-9404
    DOI 10.1007/s00280-022-04423-5
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  3. Article ; Online: Assessment of the potential of the MET inhibitor tepotinib to affect the pharmacokinetics of CYP3A4 and P-gp substrates.

    Yalkinoglu, Özkan / Becker, Andreas / Krebs-Brown, Axel / Vetter, Claudia / Lüpfert, Christian / Perrin, Dominique / Heuer, Jürgen / Biedert, Herlind / Hirt, Stefan / Bytyqi, Afrim / Bachmann, Angelika / Strotmann, Rainer

    Investigational new drugs

    2023  Volume 41, Issue 4, Page(s) 596–605

    Abstract: Tepotinib is a highly selective, potent, mesenchymal-epithelial transition factor (MET) inhibitor, approved for the treatment of non-small cell lung cancer harboring MET exon 14 skipping alterations. The aims of this work were to investigate the ... ...

    Abstract Tepotinib is a highly selective, potent, mesenchymal-epithelial transition factor (MET) inhibitor, approved for the treatment of non-small cell lung cancer harboring MET exon 14 skipping alterations. The aims of this work were to investigate the potential for drug-drug interactions via cytochrome P450 (CYP) 3A4/5 or P-glycoprotein (P-gp) inhibition. In vitro studies were conducted in human liver microsomes, human hepatocyte cultures and Caco-2 cell monolayers to investigate whether tepotinib or its major metabolite (MSC2571109A) inhibited or induced CYP3A4/5 or inhibited P-gp. Two clinical studies were conducted to investigate the effect of multiple dose tepotinib (500 mg once daily orally) on the single dose pharmacokinetics of a sensitive CYP3A4 substrate (midazolam 7.5 mg orally) and a P-gp substrate (dabigatran etexilate 75 mg orally) in healthy participants. Tepotinib and MSC2571109A showed little evidence of direct or time-dependent CYP3A4/5 inhibition (IC
    MeSH term(s) Humans ; Cytochrome P-450 CYP3A/metabolism ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism ; Midazolam/pharmacokinetics ; Cytochrome P-450 Enzyme System/genetics ; Cytochrome P-450 Enzyme System/metabolism ; Dabigatran/pharmacokinetics ; Caco-2 Cells ; Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms ; ATP Binding Cassette Transporter, Subfamily B ; Drug Interactions
    Chemical Substances Cytochrome P-450 CYP3A (EC 1.14.14.1) ; ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Midazolam (R60L0SM5BC) ; tepotinib (1IJV77EI07) ; Cytochrome P-450 Enzyme System (9035-51-2) ; Dabigatran (I0VM4M70GC) ; ATP Binding Cassette Transporter, Subfamily B ; CYP3A4 protein, human (EC 1.14.14.55)
    Language English
    Publishing date 2023-07-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604895-x
    ISSN 1573-0646 ; 0167-6997
    ISSN (online) 1573-0646
    ISSN 0167-6997
    DOI 10.1007/s10637-023-01378-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1823: Show issues Location:
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  4. Article ; Online: Exposure-response analyses for the MET inhibitor tepotinib including patients in the pivotal VISION trial: support for dosage recommendations.

    Xiong, Wenyuan / Hietala, Sofia Friberg / Nyberg, Joakim / Papasouliotis, Orestis / Johne, Andreas / Berghoff, Karin / Goteti, Kosalaram / Dong, Jennifer / Girard, Pascal / Venkatakrishnan, Karthik / Strotmann, Rainer

    Cancer chemotherapy and pharmacology

    2022  Volume 90, Issue 1, Page(s) 53–69

    Abstract: Purpose: Tepotinib is a highly selective MET inhibitor approved for treatment of non-small cell lung cancer (NSCLC) harboring METex14 skipping alterations. Analyses presented herein evaluated the relationship between tepotinib exposure, and efficacy and ...

    Abstract Purpose: Tepotinib is a highly selective MET inhibitor approved for treatment of non-small cell lung cancer (NSCLC) harboring METex14 skipping alterations. Analyses presented herein evaluated the relationship between tepotinib exposure, and efficacy and safety outcomes.
    Methods: Exposure-efficacy analyses included data from an ongoing phase 2 study (VISION) investigating 500 mg/day tepotinib in NSCLC harboring METex14 skipping alterations. Efficacy endpoints included objective response, duration of response, and progression-free survival. Exposure-safety analyses included data from VISION, plus four completed studies in advanced solid tumors/hepatocellular carcinoma (30-1400 mg). Safety endpoints included edema, serum albumin, creatinine, amylase, lipase, alanine aminotransferase, aspartate aminotransferase, and QT interval corrected using Fridericia's method (QTcF).
    Results: Tepotinib exhibited flat exposure-efficacy relationships for all endpoints within the exposure range observed with 500 mg/day. Tepotinib also exhibited flat exposure-safety relationships for all endpoints within the exposure range observed with 30-1400 mg doses. Edema is the most frequently reported adverse event and the most frequent cause of tepotinib dose reductions and interruptions; however, the effect plateaued at low exposures. Concentration-QTc analyses using data from 30 to 1400 mg tepotinib resulted in the upper bounds of the 90% confidence interval being less than 10 ms for the mean exposures at the therapeutic (500 mg) and supratherapeutic (1000 mg) doses.
    Conclusions: These analyses provide important quantitative pharmacologic support for benefit/risk assessment of the 500 mg/day dosage of tepotinib as being appropriate for the treatment of NSCLC harboring METex14 skipping alterations.
    Registration numbers: NCT01014936, NCT01832506, NCT01988493, NCT02115373, NCT02864992.
    MeSH term(s) Carcinoma, Non-Small-Cell Lung/pathology ; Edema ; Humans ; Lung Neoplasms/pathology ; Mutation ; Piperidines ; Protein Kinase Inhibitors/adverse effects ; Proto-Oncogene Proteins c-met/genetics ; Pyridazines ; Pyrimidines
    Chemical Substances Piperidines ; Protein Kinase Inhibitors ; Pyridazines ; Pyrimidines ; tepotinib (1IJV77EI07) ; Proto-Oncogene Proteins c-met (EC 2.7.10.1)
    Language English
    Publishing date 2022-06-30
    Publishing country Germany
    Document type Clinical Trial ; Journal Article
    ZDB-ID 6820-2
    ISSN 1432-0843 ; 0344-5704 ; 0943-9404
    ISSN (online) 1432-0843
    ISSN 0344-5704 ; 0943-9404
    DOI 10.1007/s00280-022-04441-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1420: Show issues Location:
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  5. Article ; Online: Molecular basis and clinical features of nephrogenic diabetes insipidus.

    Schulz, Angela / Römpler, Holger / Mitschke, Doreen / Thor, Doreen / Schliebe, Nicole / Hermsdorf, Thomas / Strotmann, Rainer / Sangkuhl, Katrin / Schöneberg, Torsten

    Expert review of endocrinology & metabolism

    2019  Volume 1, Issue 6, Page(s) 727–741

    Abstract: Maintenance of water and electrolyte homeostasis is central to mammalian survival and, therefore, under stringent hormonal control. Water homeostasis is achieved by balancing fluid intake with water excretion, governed by the antidiuretic action of ... ...

    Abstract Maintenance of water and electrolyte homeostasis is central to mammalian survival and, therefore, under stringent hormonal control. Water homeostasis is achieved by balancing fluid intake with water excretion, governed by the antidiuretic action of arginine vasopressin. Arginine vasopressin stimulation of renal V
    Language English
    Publishing date 2019-02-12
    Publishing country England
    Document type Journal Article
    ISSN 1744-8417
    ISSN (online) 1744-8417
    DOI 10.1586/17446651.1.6.727
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  6. Article ; Online: Correction: Lithium Therapy in Old Age: Recommendations from a Delphi Survey.

    Christl, Julia / Müller-Oerlinghausen, Bruno / Bauer, Michael / Kamp, Daniel / Fußer, Fabian / Benninghoff, Jens / Fehrenbach, Rosa A / Lange-Asschenfeldt, Christian / Rapp, Michael / Ibach, Bernd / Schaub, Rainer / Wollmer, Axel / Strotmann-Tack, Timm / Hüll, Michael / Biermann, Susanne / Roscher, Katharina / Meissnest, Bernd / Menges, Alexander / Weigel, Bernd /
    Maliszewski-Makowka, Dorothee / Mauerer, Christian / Schaefer, Martin / Joachimsmeier, Beate / Kayser, Sarah / Rump, Lars Christian / Supprian, Tillmann

    Pharmacopsychiatry

    2023  Volume 56, Issue 5, Page(s) e1

    Language English
    Publishing date 2023-08-30
    Publishing country Germany
    Document type Journal Article ; Published Erratum
    ZDB-ID 605670-2
    ISSN 1439-0795 ; 0720-4280 ; 0176-3679
    ISSN (online) 1439-0795
    ISSN 0720-4280 ; 0176-3679
    DOI 10.1055/a-2158-9744
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 481: Show issues Location:
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  7. Conference proceedings: Successful IL17-targeted therapy in a patient with severe Blau syndrome and novel NOD2 mutation

    Rieber, Nikolaus / Steinhauser, Maximilian / Klopfer, Matthias / Pietzsch, Sabine / Strotmann, Peter / Engelhardt, Harald / Berendes, Rainer / Burdach, Stefan

    2019  , Page(s) KR.34

    Event/congress 47. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 33. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 29. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR); Dresden; ; Gesellschaft für Kinder- und Jugendrheumatologie; 2019
    Keywords Medizin, Gesundheit
    Publishing date 2019-10-08
    Publisher German Medical Science GMS Publishing House; Düsseldorf
    Document type Conference proceedings
    DOI 10.3205/19dgrh193
    Database German Medical Science

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  8. Article ; Online: Lithium Therapy in Old Age: Recommendations from a Delphi Survey.

    Christl, Julia / Müller-Oerlinghausen, Bruno / Bauer, Michael / Kamp, Daniel / Fußer, Fabian / Benninghoff, Jens / Fehrenbach, Rosa A / Lange-Asschenfeldt, Christian / Rapp, Michael / Ibach, Bernd / Schaub, Rainer / Wollmer, Axel / Strotmann-Tack, Timm / Hüll, Michael / Biermann, Susanne / Roscher, Katharina / Meissnest, Bernd / Menges, Alexander / Weigel, Bernd /
    Maliszewski-Makowka, Dorothee / Mauerer, Christian / Schaefer, Martin / Joachimsmeier, Beate / Kayser, Sarah / Rump, Lars Christian / Supprian, Tillmann

    Pharmacopsychiatry

    2023  Volume 56, Issue 5, Page(s) 188–196

    Abstract: Introduction: While lithium (Li) has been well established for the treatment of bipolar disorder, geriatric patients require special attention when it comes to issues of drug safety. Declining renal function, amongst other medical conditions, and ... ...

    Abstract Introduction: While lithium (Li) has been well established for the treatment of bipolar disorder, geriatric patients require special attention when it comes to issues of drug safety. Declining renal function, amongst other medical conditions, and polypharmacy may pose increased risks. Only a few previous studies have addressed the management of Li in geriatric patients.
    Methods: Twenty-four German medical experts on geriatric medicine and Li treatment participated in a Delphi survey, consisting of two rounds of questionnaires and a final formulation of treatment recommendations. Three major issues of Li therapy were outlined: initiation of treatment, monitoring of ongoing therapy, and withdrawal due to medical reasons. Final recommendations were consented to at a threshold of at least 80% expert agreement.
    Results: Final consensus was achieved on 21 clinical recommendations. The approved recommendations covered aspects of necessary laboratory checks, concomitant medication, and target Li serum concentration in geriatric patients. Concerning the termination of Li therapy, an agreement was reached on the appropriate time span for tapering and on potential alternatives to Li. No consensus was achieved on whether concomitant dementia or frailty should be considered contraindications for Li treatment and the appropriate threshold of the estimated glomerular function rate for withdrawing Li.
    Conclusion: According to the view of German experts, Li may be used in geriatric patients, but it should be monitored carefully. However, the lack of consent in several specific treatment situations underlines the need for research on specific issues of Li therapy.
    MeSH term(s) Humans ; Aged ; Lithium/therapeutic use ; Bipolar Disorder/drug therapy ; Consensus ; Polypharmacy ; Lithium Compounds/adverse effects
    Chemical Substances Lithium (9FN79X2M3F) ; Lithium Compounds
    Language English
    Publishing date 2023-07-28
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 605670-2
    ISSN 1439-0795 ; 0720-4280 ; 0176-3679
    ISSN (online) 1439-0795
    ISSN 0720-4280 ; 0176-3679
    DOI 10.1055/a-2117-5200
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 481: Show issues Location:
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  9. Article: [No title information]

    Christl, Julia / Müller-Oerlinghausen, Bruno / Bauer, Michael / Kamp, Daniel / Fußer, Fabian / Benninghoff, Jens / Fehrenbach, Rosa A. / Lange-Asschenfeldt, Christian / Rapp, Michael / Ibach, Bernd / Schaub, Rainer / Wollmer, Axel / Strotmann-Tack, Timm / Hüll, Michael / Biermann, Susanne / Roscher, Katharina / Meissnest, Bernd / Menges, Alexander / Weigel, Bernd /
    Maliszewski-Makowka, Dorothee / Mauerer, Christian / Schaefer, Martin / Joachimsmeier, Beate / Kayser, Sarah / Rump, Lars Christian / Supprian, Tillmann

    Pharmacopsychiatry

    2023  Volume 56, Issue 05, Page(s) e1–e1

    Language English
    Publishing date 2023-08-30
    Publisher Georg Thieme Verlag
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 605670-2
    ISSN 1439-0795 ; 0176-3679 ; 0720-4280
    ISSN (online) 1439-0795
    ISSN 0176-3679 ; 0720-4280
    DOI 10.1055/a-2158-9744
    Database Thieme publisher's database

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 481: Show issues Location:
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  10. Book ; Thesis: Wirkung einer einwöchigen Behandlung mit Ticlopidin und Acetylsalicylsäure auf die Thrombogene Membrantransformation von Humanthrombozyten

    Strotmann, Rainer

    Vergleich diabetischer und stoffwechselgesunder Probanden

    1997  

    Author's details vorgelegt von Rainer Strotmann
    Language German
    Size 1 Mikrofiche, graph. Darst
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Univ., Diss.--Düsseldorf, 1998
    Database Former special subject collection: coastal and deep sea fishing

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