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Visar resultat 1 - 5 av 11 avhandlingar som matchar ovanstående sökkriterier.

  1. 1. Pharmacokinetic studies on cladribine

    Författare :Synnöve Lindemalm; Karolinska Institutet; Karolinska Institutet; []
    Nyckelord :;

    Sammanfattning : The aims of the present study were to delineate the pharmacokinetics, in plasma and leukaemia cells, of cladribine (M), and to describe factors influencing the outcome of administration of CdA in order to individualize and optimize treatment. CdA is a nucleoside analogue with a cytotoxic activity in low-grade lymphoproliferative disorders and childhood acute myelogenous leukaemia. LÄS MER

  3. 2. Longitudinal Models for Quantifying Disease and Therapeutic Response in Multiple Sclerosis

    Författare :Ana M. Novakovic; Mats O. Karlsson; Etienne Pigeolet; Uppsala universitet; []
    Nyckelord :MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; nonlinear mixed-effects models; pharmacometrics; NONMEM; multiple sclerosis; cladribine; EDSS; item response theory; relapse rate; absolute lymphocyte count; total volume T2 lesions; burden of disease; power; sample size; Pharmaceutical Science; Farmaceutisk vetenskap;

    Sammanfattning : Treatment of patients with multiple sclerosis (MS) and development of new therapies have been challenging due to the disease complexity and slow progression, and the limited sensitivity of available clinical outcomes. Modeling and simulation has become an increasingly important component in drug development and in post-marketing optimization of use of medication. LÄS MER

  4. 3. Studies on methotrexate and cladribine : bioanalytical, pharmacokinetic, and clinical aspects

    Författare :Freidoun Albertioni; Karolinska Institutet; Karolinska Institutet; []
    Nyckelord :;

    Sammanfattning : The aim of these studies was to delineate the pharmacokinetics of methotrexate (MTX) and cladribine in order to improve the basis for individualization and optimization of treatment with these two antimetabolites. Methodological aspects of MTX assays in clinical routine usage were investigated as plasma MTX determinations are mandatory in the high-dose treatment of childhood acute Iymphoblastic leukemia (ALL). LÄS MER

  5. 4. The role of 5'-nucleotidases and deoxynucleoside kinases in responses to nucleoside analogues

    Författare :Saeedeh Mirzaee; Karolinska Institutet; Karolinska Institutet; []
    Nyckelord :;

    Sammanfattning : The efficacy of nucleoside analogues (NAs) in treating several hematological malignancies, solid tumors and viral infections is limited primarily by side-effects and the development of drug resistance. The aims of the present thesis were to elucidate mechanism(s) involved in tissue-specific toxicity associated with NA therapy, as well as the mechanisms underlying resistance to these drugs. LÄS MER

  7. 5. Application of In Vitro Chemosensitivity Testing for Evaluation of New Cytotoxic Drugs in Chronic Lymphocytic Leukaemia

    Författare :Anna Åleskog; Jan Liliemark; Uppsala universitet; []
    Nyckelord :MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; Clinical drug development; chronic lymphocytic leukaemia; cytotoxicity; in vitro assay; cytotoxic drug development; CHS 828; IgVH mutation status; Klinisk läkemedelsutveckling; Pharmaceutical chemistry; Läkemedelskemi; Clinical Pharmacology; klinisk farmakologi;

    Sammanfattning : Despite major advances in the understanding of the biology of chronic lymphocytic leukaemia (CLL), progress in improving its treatment has been limited and it still remains an incurable disorder. In the present research, we have performed in vitro drug sensitivity testing of primary CLL cells for preclinical evaluation of cytotoxic drugs, using the fluorometric microculture cytotoxicity assay (FMCA). LÄS MER