BIOEQUIVALENCE STUDY OF TWO ORAL FORMULATIONS OF METAMIZOLE 500 MG IN HEALTHY VOLUNTEERSAbstract
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
Dhaneshwar Shep *, Rakesh Ojha, Rajeshwari Rathod , Sweta Patel , Manish Nivsarkar , Sanjay Maroo and Harish Padh
Sr. Manager, Medical Services, Troikaa Pharmaceuticals Ltd, Commerce House-1, Satya Marg, Bodakdev, Ahmedabad – 54, Gujarat, India
16 February, 2012
24 May, 2012
28 May, 2012
01 June, 2012