Asparaginase pharmacology: challenges still to be faced
作者： Claudia Lanvers-Kaminsky
DOI: 10.1007/S00280-016-3236-Y
关键词: Asparaginase 、 Medicine 、 Pharmacology toxicology 、 Biomarker (medicine) 、 Pharmacology 、 Pharmacodynamics
摘要: The benefits of asparaginase (ASNASE) in the treatment ALL and NHL are indisputable new ASNASE preparations under clinical development to overcome limitations actual therapy, especially immunogenicity. Apart from further indications preclinically clinically evaluated. We reviewed literature focused on mechanism action, biomarker, which determine sensitivity resistance, pharmacodynamics vivo. More than 40 years after introduction its action is yet not fully understood. Studies asparagine synthetase (ASNS) as biomarker for resistance contradictory complicated by methodological obstacles. role glutamine hydrolysis efficacy still debated, other mechanisms possibly identified. In addition, individual pharmacokinetic/-dynamic relationships cannot be properly addressed because limitations. sophisticated preclinical models suitable methods monitoring urgently needed (1) understand (2) establish valid biomarkers (3) evaluate pharmacokinetics/-dynamics ASNASEs patients, (4) compare bioequivalence established, well preparations.
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