Simulation of Remdesivir Pharmacokinetics and Its Drug Interactions

Purpose: Remdesivir, a drug originally developed against Ebola virus, is currently recommended for patients hospitalized with coronavirus disease of 2019 (COVID-19). In spite United States Food and Drug Administration’s recent assent remdesivir as the only approved agent COVID-19, there limited information available about physicochemical, metabolism, transport, pharmacokinetic (PK), drug-drug interaction (DDI) properties this drug. The objective in silico simulation work was to simulate biopharmaceutical DDI behavior characterize PK special populations which are highly affected by COVID-19. Methods: Spatial Data File format structures prodrug (GS-5734) nucleoside core (GS-441524) were obtained from PubChem database upload into GastroPlus software 9.8 version (Simulations Plus Inc., USA). Absorption, Distribution, Metabolism, Excretion Toxicity (ADMET) Predictor PKPlus modules used physicochemical properties, respectively, healthy predisposed patients. Physiologically based (PBPK) modeling different patient on age, weight, liver function, renal function status. Subsequently, these data Drug-Drug Interaction module potential other COVID-19 regimens agents comorbidities. Results: Remdesivir more hydrophilic than inactive demonstrating better water solubility. GS-5734, but not GS-441524, predicted be metabolized CYP3A4. bioavailable its clearance achieved through hepatic routes. Differential effects or age observed profile remdesivir. study perpetrator drugs comorbidities indicate that carbamazepine, phenytoin, amiodarone, voriconazole, diltiazem, verapamil have strong interactions victim remdesivir, whereas treatment such chloroquine ritonavir can cause weak interactions, Conclusions: GS-5734 (inactive prodrug) appears superior derivative due stability, optimum hydrophilic/lipophilic balance, disposition properties. potentially physiological pathological conditions, version. PredictorTM PKPlusTM InteractionTM commodities.