ANALYTICAL METHOD VALIDATION, PHARMACOKINETICS AND BIOEQUIVALENCE STUDY OF DIMETHYL FUMARATE IN HEALTHY IRANIAN VOLUNTEERS

GHASEMIAN ELHAM; SADRAI SIMA; SHOKRI JAVAD; SAYADI SHAHRAM

doi:10.22159/ijpps.2021v13i9.42328

Authors

GHASEMIAN ELHAM Department of Pharmaceutics, Faculty of Pharmacy, Islamic Azad University of Damghan, Damghan, Iran
SADRAI SIMA Division of Biopharmaceutics and Pharmacokinetics, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
SHOKRI JAVAD Pharmaceutical department, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
SAYADI SHAHRAM Anesthesiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

DOI:

https://doi.org/10.22159/ijpps.2021v13i9.42328

Keywords:

Bioequivalent, Pharmacokinetics, Multiple sclerosis, Dimethyl fumarate, LC-MS/MS

Abstract

Objective: Pharmacokinetic evaluation of Dimethyl Fumarate (DMF) in the Iranian population wasn’t studied. So, the aim of this research is the validation of the analytical method and evaluation of the pharmacokinetic properties and bioequivalence of the generic form of this drug versus the reference product.

Methods: 2 single-dose, test, and reference DMF products were orally administered to 24 healthy volunteers. The washout period was 28 d between the treatments. Monomethyl fumarate as the metabolite of DMF was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the method was validated. Also, the pharmacokinetic parameters were calculated for bioequivalence evaluation.

Results: The analytical method was validated and linear over the range of 31.25-4000 ng/ml (R²= 0.997). In addition, the method was precise and accurate in the low, medium, and high concentrations. The results indicated that the 2 products had similar pharmacokinetics. Further, the 90% CI of the mean ratios of the test versus the reference products of the log-transformed area under the concentration-time curve over 10 h (0.99 to 1.02) and peak concentration (0.98 to 1.03) were within the acceptable range of 0.8 to 1.25 and the generic product of DMF could be similar to that of the reference product.

Conclusion: The applied analytical method is selective, accurate, precise, and repeatable for the analysis of monomethyl fumarate (MMF) in plasma. Also, the bioequivalence study showed no significant difference between the pharmacokinetic parameters of these 2 products. So, the DMF test product can be claimed to be bioequivalent with the reference product.

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