title: Comparative study of the anti-leukemic effects of imatinib mesylate, Glivec™ tablet and its generic formulation, OHK9511.
abstract: Long-term treatment with imatinib mesylate (IM) allows patients with chronic myeloid leukemia (CML) to live a near-normal lifespan. However, the fact that tyrosine kinase inhibitors, including IM, are extremely expensive is a major cause of poor adherence, resulting in disease relapse or drug resistance. Therefore, physicians are encouraged to prescribe generic drugs to reduce the financial burden of medical expenses. In Japan, only generic drugs that have a basic chemical structure and pharmacokinetic data that are the same as those of the original drug are approved. However, it is not mandatory to demonstrate that generic drugs have adequate biological effects. This is one of the reasons why Japanese hematologists do not often use generic IM. The aim of the present study was to compare the anti-leukemic effects of Glivec™ (a commercial IM) and its generic formulation, OHK9511. The IC50 values of OHK9511 and Glivec™ were comparable, and both induced similar levels of apoptosis in several CML cell lines. Furthermore, the overall survival of OHK9511-treated mice transplanted with BCR-ABL-positive cells was similar to that of mice treated with Glivec™. Although the experiments performed herein were basic, the results suggest that physicians should consider using generic IM.
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University.
authors.forename: Masako
authors.initials: M
authors.lastname: Yokoo
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kubota
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tabe
authors.forename: Shinya
authors.initials: S
authors.lastname: Kimura
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm; D016568:Drugs, Generic / Q000494:pharmacology* / Q000627:therapeutic use; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D000068877:Imatinib Mesylate / Q000494:pharmacology* / Q000627:therapeutic use; D020128:Inhibitory Concentration 50; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism; D055118:Medication Adherence; D008698:Mesylates / Q000494:pharmacology / Q000627:therapeutic use; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013607:Tablets
chemical_list: D000970:Antineoplastic Agents; D016568:Drugs, Generic; D008698:Mesylates; D047428:Protein Kinase Inhibitors; D013607:Tablets; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl