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Pharmaceutics

(96) A Pharmacokinetic Modeling Approach to Evaluate the Current Dosing Recommendations for Molnupiravir in Egyptian Population

    Primary Author(s)

  • AA

    Ahmed M. Ali

    Assistant Professor
    Notre Dame of Maryland University
    Baltimore, Maryland, United States

    • Co-Author(s)

  • AM

    Ahmed M. Salem

    PhD Candidate
    University of Maryland Baltimore, United States

  • AS

    Amira S. Gouda

    PhD candidate
    Zi diligence Biocenter, Cairo, Egyp, United States

  • HM

    Hoda M. Marzouk

    Assistant Professor
    Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt, United States

  • MR

    Mamdouh R. Rezk

    Professor
    Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt, United States

Objective : Molnupiravir, a prodrug of the antiviral N-hydroxycytidine (NHC), is one of the limited treatment options that has recently gained emergency use authorization by the US FDA for treating mild-to-moderate SARS-CoV-2 cases. Middle Eastern Populations show distinct Genetic Makeup in Drug Metabolizing Enzymes which could lead to different exposures compared to other ethnic groups. While NHC is shown to follow linear pharmacokinetics with similar exposures in healthy and SARS-CoV-2 subjects, its pharmacokinetics has not been characterized in the Egyptian population.

Methods: Twelve healthy volunteers received 800 mg molnupiravir oral dose.
Model development using non-linear mixed effect modeling and internal validation using bootstrapping and visual predictive check were conducted in MonolixSuite.
Simulation-based maximum concentration (Cmax) "the safety metric" and area under the curve (AUC0-12h) "the efficacy metric" were computed for 1000 virtual subjects.
Geometric mean ratios (GMR) and 90% confidence intervals (CI) compared to previously reported values were calculated

Results: Our simulations showed that the median Cmax, the PK metric for safety, and AUC0-12, the PK metric for efficacy, were 3827 ng/mL and 9320 ng.h/mL, respectively. The simulations are comparable to previous analysis where the reported values for both PK metrics were 3640 ng/mL and 8720 ng.h/mL following the administration of 800 mg of Molnupiravir. Consequently, the current dosing recommendations of MOL are sufficient to ensure efficacy and safety in the Egyptian population.

Conclusions: Population pharmacokinetic model was developed for NHC.
Simulations showed that current molnupiravir dosage can achieve the therapeutic targets and dose adjustment may not be required for the Egyptian population.
The developed model could be used in the future to refine molnupiravir's dosage once further therapeutic targets are identified