Bioequivalence Study of Two Oral Formulations of Metamizole 500 Mg in Healthy Volunteers

Background: Metamizole (Dipyrone) is widely used and has effective analgesic, antipyretic, and antispasmodic properties. After oral or intravenous administration, dipyrone is rapidly hydrolyzed to the active moiety 4-methylaminoantipyrine. Aim: The aim of this study was to assess the bioequivalence of 2 oral formulations of Metamizole 500 mg. Methods: This double blind, randomized, single-dose, 2-period crossover study in healthy Indian adult volunteers was conducted at PERD Centre, Ahmedabad. Subjects received Metamizole 500 mg of either test or reference formulation with a washout period of 7 days. After study drug administration, serial blood samples were collected over a period of 24 hours. Plasma concentration of 4-methylaminoantipyrine was measured by pre-validated LC-MS method. Pharmacokinetic (PK) parameters Cmax, Tmax, t1/2, AUC0-t, AUC0-∞, and kel, were determined for test and reference formulations. The formulations were to be considered bioequivalent if the log-transformed ratios of Cmax, AUC0-t, and AUC0-∞ were within the predetermined bioequivalence range of 80% to 125%. Results: A total of 14 subjects were enrolled. No significant differences were found based on analysis of variance, with mean values and 90% confidence intervals of test/reference ratios for these parameters as follows: Cmax, 18.24 versus 18.44 μg/mL (92.68 106.61); AUC0-t, 92.97 Versus 91.37 μg.hr/mL (89.49 113.09); and AUC0-∞, 96.64 Versus 94.65 μg.hr/mL (92.31 111.63). Conclusion: Since the 90% confidence intervals for Cmax, AUC0-t, and AUC0−∞ were within the interval of 80-125%, it was concluded that both formulations were bioequivalent, according to both the rate and extent of absorption. INTRODUCTION: Dipyrone (metamizole) is widely used and has effective analgesic, antipyretic, and antispasmodic properties. The drug is indicated for severe pain conditions, especially those associated with smooth muscle spasm or colics affecting the gastrointestinal, biliary, or urinary tracts . Moreover, dipyrone is useful for treatment of cancer pain and migraine as well as fever refractory to other treatments. Dipyrone is a prodrug, and its pharmacokinetics has been extensively investigated 2, . After oral or intravenous administration, dipyrone is rapidly hydrolyzed to the active moiety 4-methylamino antipyrine (MAA) 4, .