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. 2023 Oct 3;24(7):204.
doi: 10.1208/s12249-023-02660-2.

Bioequivalence Evaluation of Topical Metronidazole Products Using Dermal Microdialysis in New Zealand Rabbits

Sharareh Senemar  1 , Benjamin A Kuzma  1   2 , Tannaz Ramezanli  3 , Priyanka Ghosh  3 , Sam G Raney  3 , Elena Rantou  4 , Grazia Stagni  5
Affiliations

Bioequivalence Evaluation of Topical Metronidazole Products Using Dermal Microdialysis in New Zealand Rabbits

Sharareh Senemar et al. AAPS PharmSciTech. .

Abstract

Comparative assessment of cutaneous pharmacokinetics (cPK) by dermal microdialysis (dMD) appears to be suitable to evaluate the bioequivalence (BE) of topical dermatological drug products applied to the skin (TDDPs). Although dMD studies in the literature have reported inconclusive BE assessments, we have addressed several methodological deficiencies to improve dMD's capability to assess BE between reference (R) and approved generic (referred to as test (T)) gel and cream products of metronidazole (MTZ). The 90% confidence interval (CI) of the geometric mean ratios for the Ln(AUC0-24) and Ln(Cmax) endpoints was centered within the BE limits of 80-125%. The CIs extended outside this range as the proof-of-principle study was not statistically powered to demonstrate BE (N = 7 rabbits). A power analysis suggests that, with the variability observed in this study, 21 rabbits for the cream and 11 rabbits for the gel would be sufficient to support an evaluation of BE with the 2 probe replicates we used, and only 10 and 5 rabbits would be sufficient to power the study for the cream and gel, respectively, if 4 probe replicates are used for each treatment per rabbit. These results indicate that dMD when properly controlling variables can be used to support BE assessments for TDDPs.

Keywords: bioavailability; bioequivalence; cutaneous pharmacokinetics; dermal microdialysis; metronidazole.

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References

    1. Yacobi A, Shah VP, Bashaw ED, Benfeldt E, Davit B, Ganes D, et al. Current challenges in bioequivalence, quality, and novel assessment technologies for topical products. Pharm Res. 2014;31(4):837–46. https://doi.org/10.1007/s11095-013-1259-1 . - DOI - PubMed
    1. Ramezanli T. Bioequivalence of Topical Products: Scientific Considerations. 4th FDA/PQRI Conference on Advancing Product Quality. 2019.
    1. Raney SG, Luke MC. A new paradigm for topical generic drug products: impact on therapeutic access. 2020. p. 1570–1. https://doi.org/10.1016/j.jaad.2020.01.062 .
    1. Karimkhani C, Dellavalle RP, Coffeng LE, Flohr C, Hay RJ, Langan SM, et al. Global Skin Disease Morbidity and Mortality: an update From the Global Burden of Disease Study 2013. JAMA Dermatol. 2017;153(5):406–12. https://doi.org/10.1001/jamadermatol.2016.5538 . - DOI - PubMed - PMC
    1. Davit BM, Chen ML, Conner DP, Haidar SH, Kim S, Lee CH, et al. Implementation of a reference-scaled average bioequivalence approach for highly variable generic drug products by the US Food and Drug Administration. AAPS J. 2012;14(4):915–24. https://doi.org/10.1208/s12248-012-9406-x . - DOI - PubMed - PMC

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