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

• Published in: Biological & pharmaceutical bulletin Vol. 38; no. 3; pp. 411 - 416
• Main Authors: Yokoo, Masako, Kubota, Yasushi, Tabe, Yoko, Kimura, Shinya
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.03.2015; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: adherence; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; chronic myeloid leukemia; Drug Resistance, Neoplasm; Drugs, Generic - pharmacology; Drugs, Generic - therapeutic use; Fusion Proteins, bcr-abl - metabolism; generic; imatinib mesylate; Imatinib Mesylate - pharmacology; Imatinib Mesylate - therapeutic use; Inhibitory Concentration 50; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism; Medication Adherence; Mesylates - pharmacology; Mesylates - therapeutic use; Mice, Inbred BALB C; Mice, Nude; OHK9511; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Tablets
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b14-00652

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.