Publications by authors named "Keisuke Gotanda"
Aims: Crovalimab is a novel C5 inhibitor administered first intravenously and then subcutaneously in patients with paroxysmal nocturnal haemoglobinuria (PNH) naive to complement inhibition or switching from eculizumab or ravulizumab. Crovalimab showed efficacy and safety comparable to eculizumab in the pivotal COMMODORE 2 and supporting studies.
Methods: We characterized crovalimab pharmacokinetics and the relationship between exposure pharmacokinetic parameters and pharmacodynamic biomarkers, efficacy and safety endpoints using pooled data (healthy volunteers [n = 9], naive [n = 210] and switched [n = 211] patients).
Article Synopsis
- Drug-target-drug complexes (DTDCs) were observed in patients transitioning from eculizumab to crovalimab for treating paroxysmal nocturnal hemoglobinuria (PNH), due to the different ways these drugs bind to C5.
- In a phase I/II study, patients experienced transient reductions in crovalimab levels and the formation of DTDCs, with some mild hypersensitivity reactions noted.
- A mathematical model helped optimize crovalimab dosing, resulting in over a 50% reduction of large DTDCs and improved safety, showing that careful dosing can enhance treatment outcomes for patients using new antibody therapies.
Article Synopsis
- - A variant in the BCRP gene (421C>A) helps explain differences in how individuals metabolize the drug sulfasalazine (SASP), but there are still variations among people with the same genetic variant.
- - Researchers propose that levels of exosomal miR-328, found in plasma and influenced by intestinal leakage, could serve as a biomarker for assessing the activity of BCRP in the intestines.
- - In a study with 33 healthy participants, higher levels of intestine-derived miR-328 were linked to increased SASP exposure, indicating lower BCRP activity, highlighting its potential as a biomarker for BCRP function.
Purpose: Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), and bevacizumab, an anti-vascular endothelial growth factor (VEGF) agent, are promising therapies for advanced non-small cell lung cancer (NSCLC). Our study was aimed to determine whether there were conditions under which the addition of bevacizumab would enhance the antitumor activity of erlotinib against NSCLC tumors in vitro and in vivo.
Methods: MTS was for NSCLC cell (PC9, 11-18, H1975, H157, H460 and A549) growth assay in vitro.
Aims: HMG-CoA reductase inhibitors are available for use in low density lipoprotein-cholesterol (LDL-C) lowering therapy. The purposes of this study were to develop a population pharmacodynamic (PPD) model to describe the time course for the LDL-C lowering effects of statins and assess the efficacy of combination therapy based on electronic medical records.
Methods: Patient backgrounds, laboratory tests and prescribed drugs were collected retrospectively from electronic medical records.
Background: Thymidylate synthase (TYMS) is an important folate-dependent enzyme in DNA synthesis and an important target for cancer chemotherapy. High TYMS expression levels in tumors are generally associated with resistance to 5-fluorouracil (5-FU). The cause of the variability in TYMS expression is still not fully understood, however, only a small proportion of the TYMS expression can be explained by TYMS genetic polymorphisms.
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