Physiologically Based Pharmacokinetic Modelling to Investigate the Impact of the Cytokine Storm on CYP3A Drug Pharmacokinetics in COVID-19 Patients.

ABSTRACT: Patients with coronavirus disease 2019 (COVID-19) may experience a cytokine storm with elevated interleukin-6 (IL-6) levels in response to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). IL-6 suppresses hepatic enzymes, including CYP3A; however, the effect on drug exposure and drug-drug interaction magnitudes of the cytokine storm and resulting elevated IL-6 levels have not been characterized in patients with COVID-19. We used physiologically-based pharmacokinetic (PBPK) modeling to simulate the effect of inflammation on the pharmacokinetics of CYP3A metabolized drugs. A PBPK model was developed for lopinavir boosted with ritonavir (LPV/r), using clinically observed data from people living with HIV (PLWH). The inhibition of CYPs by IL-6 was implemented by a semimechanistic su

SUBMITTER: Stader F 

PROVIDER: S-EPMC8652944 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature