Bioequivalence study of a generic formulation of imatinib mesylate 400 mg filmcoated tablets versus Glivec® : a randomized open-label trial, single-dose, fasting, two-period, two-sequence crossover comparison in healthy Colombian volunteers.
Estudio de bioequivalencia de una formulación genérica de tabletas recubiertas de imatinib mesilato por 400 mg versus Glivec® : un estudio comparativo, aleatorizado, abierto, de dosis única, en ayunas, de dos períodos, en dos secuencias cruzadas en volunt
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Objective: To compare bioavailability of two different imatinib pharmaceutical formulations to establish bioequivalency, according to FDA regulation. Methods: A single-dose, randomized open-label trial was performed, fasting, in two periods and two complete cross sequences with an 8-day washout period. All the study subjects were from Colombia. Imatinib blood levels were measured from plasma samples using high-efficiency liquid chromatography (HPLC) with an UV-light detector. Results: Healthy volunteers representative of Colombian population and racial types were included with a mean age of 25 years (range 18-40) and a mean body mass index (BMI) of 22 kg/m2 (range 19-24,9). Test product Cmax, Tmax and AUC (0-t) were 1437,2 ng/ml, 3,4 hours and 20431.5 ng.h/ml. Meanwhile reference product Cmax, Tmax and AUC Inf was 1435,9 ng/ml, 3,4 hours and 21296,5 ng.h/ml, respectively. Test/reference product ratios for Cmax, AUC (0-t) and AUC (0-inf) were 1,002 (CI 90% 0,903-1,112), 1,072 (CI 90% 0,935-1,230) and 1,029 (CI 90% 0,914-1,158), respectively. Conclusion: Test product (Imatin®, Procaps) and reference product (Glivec®, Novartis) are bioaquivalente according to FDA-established regulation.
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Miura M, Takahashi N, Sawada K. Quantitative determination of imatinib in human plasma with high-performance liquid chromatography and ultraviolet detection. J Chromatogr Sci. 2011;49(5):412-5.
Hillberg P. Development of a quantitative chromatographic method for the determination of imatinib and its main metabolite in human plasma. Department of Physics, Chemistry and Biology, Linköping University; 2009.
Roth O, Spreux-Varoquaux O, Bouchet S, Rousselot P, Castaigne S, Rigaudeau S, et al. Imatinib assay by HPLC with photodiodearray UV detection in plasma from patients with chronic myeloid leukemia: Comparison with LC-MS/MS. Clin Chim Acta. 2010;411(3-4):140-6.
Golabchifar AA, Rouini MR, Shafaghi B, Rezaee S, Foroumadi A, Khoshayand MR. Optimization of the simultaneous determination of imatinib and its major metabolite, CGP74588, in human plasma by a rapid HPLC method using D-optimal experimental design. Talanta. 2011;85(5):2320-9.
Davies A, Hayes AK, Knight K, Watmough SJ, Pirmohamed M, Clark RE. Simultaneous determination of nilotinib, imatinib and its main metabolite (CGP-74588) in human plasma by ultra-violet high performance liquid chromatography. Leuk Res. 2010;34(6):702-7.
Food and Drugs Administration. Guidance for industry statistical approaches to establishing bioequivalence. 2009.
Harrison TR. Oncología y hematología. Principios de medicina interna. Chile: McGraw-Hill Interamericana; 2006.
Food and Drug Administration. Guidance for industry. Bioavailability and bioequivalence studies for orally administered drug products. General considerations. 2010.
The European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products (CPMP). Note for guidance on the investigation of bioavailability and bioequivalence. London; 2001.
Guía de biodisponibilidad y de bioequivalencia de medicamentos del 2001. Resolución 1400 (24 de agosto del 2001).
Normas científicas, técnicas y administrativas para la investigación en salud de 1993. Resolución 8430 (4 de octubre de 1993).
Establece la obligatoriedad de implementar el correspondiente programa de farmacovigilancia para todos los titulares de registro sanitario de medicamentos y productos fitoterapéuticos del 2004. Resolución 9455 (28 de mayo del 2004).
Declaración de Helsinki de la Asociación Médica Mundial. Principios éticos para las investigaciones médicas en seres humanos 2000. 52ª Asamblea General, Edimburgo, Escocia, octubre del 2000).
Gschwind HP, Pfaar U, Waldmeier F, Zollinger M, Sayer C, Zbinden P, et al. Metabolism and disposition of imatinib mesylate in healthy volunteers. Drug Metab Dispos. 2005;33(10):1503-12.
Peng B, Dutreix C, Mehring G, Hayes MJ, Ben-Am M, Seiberling M, et al. Absolute bioavailability of imatinib (Glivec) orally versus intravenous infusion. J Clin Pharmacol. 2004;44(2):158-62.
Nikolova Z, Peng B, Hubert M, Sieberling M, Keller U, Ho YY, et al. Bioequivalence, safety, and tolerability of imatinib tablets compared with capsules. Cancer Chemother Pharmacol. 2004;53(5):433-8.
Dutreix C, Peng B, Mehring G, Hayes M, Capdeville R, Pokorny R, et al. Pharmacokinetic interaction between ketoconazole and imatinib mesylate (Glivec) in healthy subjects. Cancer Chemother Pharmacol. 2004;54(4):290-4.
Bolton AE, Peng B, Hubert M, Krebs-Brown A, Capdeville R, Keller U, et al. Effect of rifampicin on the pharmacokinetics of imatinib mesylate (Gleevec, STI571) in healthy subjects. Cancer Chemother Pharmacol. 2004;53(2):102-6.
Parrillo-Campiglia S, Ercoli MC, Umpierrez O, Rodríguez P, Márquez S, Guarneri C, et al. Bioequivalence of two film-coated tablets of imatinib mesylate 400 mg: a randomized, open-label, single-dose, fasting, two-period, two-sequence crossover comparison in healthy male South American volunteers. Clin Ther. 2009;31(10):2224-32.
Queckenberg C, Fuhr U. Influence of posture on pharmacokinetics. Eur J Clin Pharmacol. 2009;65(2):109-19.
D’Avolio A, Simiele M, De Francia S, Ariaudo A, Baietto L, Cusato J, et al. HPLC-MS method for the simultaneous quantification of the antileukemia drugs imatinib, dasatinib and nilotinib in human peripheral blood mononuclear cell (PBMC). J Pharm Biomed Anal. 2012;59:109-16.
Velpandian T, Mathur R, Agarwal NK, Arora B, Kumar L, Gupta SK. Development and validation of a simple liquid chromatographic method with ultraviolet detection for the determination of imatinib in biological samples. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;804(2):431-4.
Widmer N, Béguin A, Rochat B, Buclin T, Kovacsovics T, Duchosal MA, et al. Determination of imatinib (Gleevec) in human plasma by solid-phase extraction-liquid chromatography-ultraviolet absorbance detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;803(2):285-92.
Awidi A, Salem II, Najib N, Mefleh R, Tarawneh B. Determination of imatinib plasma levels in patients with chronic myeloid leukemia by high performance liquid chromatography-ultraviolet detection and liquid chromatography-tandem mass spectrometry: methods’ comparison. Leuk Res. 2010;34(6):714-7.
Tan KL, Ankathil R, Gan SH. Method development and validation for the simultaneous determination of imatinib mesylate and Ndesmethyl imatinib using rapid resolution high performance liquid chromatography coupled with UV-detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2011;879(30):3583-91.
Martins DH, Wagner SC, Dos Santos TV, Lizot Lde L, Antunes MV, Capra M, et al. Monitoring imatinib plasma concentrations in chronic myeloid leukemia. Rev Bras Hematol Hemoter. 2011;33(4):302-6.
Wagner JG. Biopharmaceutics and relevant pharmacokinetics. 1st ed. Hamilton, IL: Drug Intelligence Publications; 1971. p. 12, 17.
Jawhari D, Al Swisi M, Ghannam M. Bioavailability of a new generic formulation of imatinib mesylate 400 mg tablets versus Glivec in healthy male adult volunteers. J Bioequiv Availab. 2011;3:161-4.
