Comparative Study of the Anti-leukemic Effects of Imatinib Mesylate, Glivec™ Tablet and Its Generic Formulation, OHK9511

Yokoo, Masako; Kubota, Yasushi; Tabe, Yoko; Kimura, Shinya

doi:10.1248/bpb.b14-00652

Cited by 5 publications

(7 citation statements)

References 31 publications

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“…Cell viability was assessed using a trypan blue dye exclusion method and cell proliferation was evaluated using a modified methyl-thiazol-diphenyl- tetrazolium (MTT) assay with SF reagent (Nacalai Tesque, Kyoto, Japan) as described previously [ 37 , 38 ]. Cells, including human primary hepatocytes (Applied Cell Biology Research Institute, Kirkland, WA, USA) were seeded in flat-bottomed 96-well plates (Greiner Labortechnik, Hamburg, Germany) at a density of 1×10 4 cells in 100 μL medium per well, and incubated with HP-β-CyD at various concentrations for 72 hours.…”

Section: Methodsmentioning

confidence: 99%

2-Hydroxypropyl-β-Cyclodextrin Acts as a Novel Anticancer Agent

et al. 2015

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2-Hydroxypropyl-β-cyclodextrin (HP-β-CyD) is a cyclic oligosaccharide that is widely used as an enabling excipient in pharmaceutical formulations, but also as a cholesterol modifier. HP-β-CyD has recently been approved for the treatment of Niemann-Pick Type C disease, a lysosomal lipid storage disorder, and is used in clinical practice. Since cholesterol accumulation and/or dysregulated cholesterol metabolism has been described in various malignancies, including leukemia, we hypothesized that HP-β-CyD itself might have anticancer effects. This study provides evidence that HP-β-CyD inhibits leukemic cell proliferation at physiologically available doses. First, we identified the potency of HP-β-CyD in vitro against various leukemic cell lines derived from acute myeloid leukemia (AML), acute lymphoblastic leukemia and chronic myeloid leukemia (CML). HP-β-CyD treatment reduced intracellular cholesterol resulting in significant leukemic cell growth inhibition through G2/M cell-cycle arrest and apoptosis. Intraperitoneal injection of HP-β-CyD significantly improved survival in leukemia mouse models. Importantly, HP-β-CyD also showed anticancer effects against CML cells expressing a T315I BCR-ABL mutation (that confers resistance to most ABL tyrosine kinase inhibitors), and hypoxia-adapted CML cells that have characteristics of leukemic stem cells. In addition, colony forming ability of human primary AML and CML cells was inhibited by HP-β-CyD. Systemic administration of HP-β-CyD to mice had no significant adverse effects. These data suggest that HP-β-CyD is a promising anticancer agent regardless of disease or cellular characteristics.

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Section: Methodsmentioning

confidence: 99%

2-Hydroxypropyl-β-Cyclodextrin Acts as a Novel Anticancer Agent

et al. 2015

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“…Yokoo et al 11 investigated the antileukemic effects of one generic imatinib on CML cell lines, and they reported comparable growth inhibitory and proapoptotic effects for both branded and generic imatinib.…”

Section: Pharmacologic Properties and Bioequivalence Of The Genericsmentioning

confidence: 99%

Current evidence on the efficacy and safety of generic imatinib in CML and the impact of generics on health care costs

Erçalışkan¹,

Erdoğan

Eşkazan³

2021

Blood Advances

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Since the introduction of imatinib, the management of chronic myeloid leukemia (CML) has changed considerably. Tyrosine kinase inhibitors (TKIs) are the mainstay of CML treatment; however, the high financial burden of TKIs can be problematic for both the patients and health care systems. After the emergence of generics, reimbursement policies of many countries have changed, and generics offered an alternative treatment option for CML patients. There are many papers published on the use of generics in CML patients with conflicting results regarding both efficacy and safety. In this paper, we systematically reviewed the current literature on generic imatinib use in CML, and 36 papers were evaluated. Both in vitro and in vivo studies of generic imatinib showed comparable results with branded imatinib in terms of bioequivalence and bioavailability. In most studies, generics were comparable with the original molecule in terms of efficacy and safety, both in newly diagnosed patients and after switching from Gleevec. Some generic studies showed contradictory findings regarding efficacy and toxicity, and these differences can be attributed to some factors including the use of different generics in different countries. Both in hypothetical models and in real life, introduction of generic imatinib caused significant reduction in health care costs. In conclusion, generics are not inferior to original imatinib in terms of efficacy with an acceptable toxicity profile. Notwithstanding the generally favorable efficacy and safety of generics worldwide to date, we most probably still need more time to draw firmer conclusions on the longer-term outcomes of generics.

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“…7,9,11 These findings have been confirmed in vitro with cell lines and in vivo in rodents. 12 The expiration dates of the BI patent vary internationally; the patent on the -crystal formulation, on which the majority of GI are based, has already expired in most countries. 7,9 According to the worldwide CML Advocates Network, which produces an unofficial online registry of TKIs, 62 GI were produced or marketed by a comparable number of pharmaceutical companies as of July 2014.…”

Section: Pharmacological Backgroundmentioning

confidence: 99%

“…Initial studies suggested that the β‐crystal form is superior with regard to efficacy and pharmacologic properties (eg, bioavailability influenced by water solubility, absorption); however, subsequent studies in adults showed no difference between the α‐ and β‐crystal forms that significantly influence the performance of GI . These findings have been confirmed in vitro with cell lines and in vivo in rodents …”

Section: Introductionmentioning

confidence: 99%

Generic formulations of imatinib for treatment of Philadelphia chromosome–positive leukemia in pediatric patients

Suttorp¹,

Metzler

Millot³

et al. 2018

Pediatric Blood & Cancer

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Since the patent for imatinib has expired, the role of generic imatinib (GI) in the management of Philadelphia chromosome-positive (Ph+) leukemia in pediatric patients has had ongoing discussion. Some studies in adults demonstrated that equivalent doses of GI and branded imatinib (BI) result in comparable plasma concentrations and clinical efficacy. However, other studies found that GI users are more likely to stop imatinib, with intolerance and decreased persistence as the main causes. Economic factors also heavily influence GI selection. This article aims to review the present knowledge to support further discussion on the role of GI in the management of pediatric Ph+ leukemia.

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Comparative Study of the Anti-leukemic Effects of Imatinib Mesylate, Glivec™ Tablet and Its Generic Formulation, OHK9511

Cited by 5 publications

References 31 publications

2-Hydroxypropyl-β-Cyclodextrin Acts as a Novel Anticancer Agent

2-Hydroxypropyl-β-Cyclodextrin Acts as a Novel Anticancer Agent

Current evidence on the efficacy and safety of generic imatinib in CML and the impact of generics on health care costs

Generic formulations of imatinib for treatment of Philadelphia chromosome–positive leukemia in pediatric patients

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