Preclinical assessment of nirmatrelvir penetration into cerebrospinal fluid and central nervous system cells and tissues

Author:

Avedissian Sean1ORCID,Malik Johid1,Podany Anthony1,Neely Michael2,Rhodes Nathaniel3ORCID,Scarsi Kimberly4ORCID,Scheetz Marc5,Duryee Michael4,Modebelu Ukamaka4,Mykris Timothy4,Winchester Lee1,Byrareddy Siddappa1ORCID,Fletcher Courtney6ORCID

Affiliation:

1. University of Nebraska Medical Center

2. University of Southern California-CHLA

3. Midwewestern University

4. UNMC

5. Midwestern University

6. University of Nebraska Medical Center, College of Pharmacy

Abstract

Abstract Three years after SARS-CoV-2 emerged as a global infectious threat, the virus has become endemic. The neurological complications such as depression, anxiety, and other CNS complications after COVID-19 disease are increasing. The brain, and CSF have been shown as viral reservoirs for SARS-CoV-2, yielding a potential hypothesis for CNS effects. Thus, we investigated the CNS pharmacology of orally dosed nirmatrelvir/ritonavir (NMR/RTV). Using both an in vitro and an in vivo rodent model, we investigated CNS penetration and potential pharmacodynamic activity of NMR. Through pharmacokinetic modeling, we estimated the median CSF penetration of NMR to be low at 18.11% of plasma with very low accumulation in rodent brain tissue. Based on the multiples of the 90% maximal effective concentration for SARS-CoV-2, concentrations in the CSF and brain may be inadequate to achieve exposure similar to that of plasma, which may have implications for viral persistence and neurologic post-acute sequelae of COVID-19.

Publisher

Research Square Platform LLC

Reference72 articles.

1. Center for Disease Control and Prevention: Coronavirus Disease 2019 (COVID-19). Cases in the U.S. Available at: cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html.

2. Johns Hopkins Coronavirus Resource Center. Last Updated (5/18/2022). Covid-10 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University.

3. [A pathological report of three COVID-19 cases by minimally invasive autopsies];Yao XH;Zhonghua Bing Li Xue Za Zhi. Mar,2020

4. COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available at https://www.covid19treatmentguidelines.nih.gov/. Accessed [12/7/2022].

5. Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy? Biomed Pharmacother;Hashemian SMR;Jun,2023

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