Pharmacokinetic analysis of antiviral drug ritonavir across the blood-brain barrier and its interaction with Scutellaria baicalensis using multisite microdialysis in rats.

Pharmacokinetic analysis of antiviral drug ritonavir across the blood-brain barrier and its interaction with Scutellaria baicalensis using multisite microdialysis in rats.

Publication date: Aug 01, 2024

Ritonavir, an excellent inhibitor of CYP3A4, has recently been combined with nirmatrelvir to form Paxlovid for the treatment of severe acute respiratory syndrome coronavirus 2 infections. The root of Scutellaria baicalensis Georgi (S. baicalensis), a traditional Chinese medicinal (TCM) herb commonly used to treat heat/inflammation in the lung and digestive tracts, which are major organs targeted by viral infections, contains flavones that can influence the CYP3A metabolism pathway. To investigate the ability of ritonavir to cross the bloodbrain barrier (BBB) and its potential herb-drug interactions with an equivalent TCM clinical dose of S. baicalensis, multisite microdialysis coupled with an LCMS/MS system was developed using rat model. Pretreatment with S. baicalensis extract for 5 days, which contains less flavones than those used in previous studies, had a significant influence on ritonavir, resulting in a 2-fold increase in the total concentration of flavones in the blood and brain. Treatment also boosted the maximum blood concentration of flavones by 1. 5-fold and the maximum brain concentration of flavones by 2-fold, all the while exerting no noticeable influence on the transfer ratio across the bloodbrain barrier. These experimental results demonstrated that the use of a typical traditional Chinese medicinal dose of S. baicalensis is sufficient to influence the metabolic pathway and synergistically increase the concentration of ritonavir in rats.

Concepts Keywords
Chinese Animals
Coronavirus Antiviral Agents
Herb Blood-Brain Barrier
Pharmacokinetic Blood‒brain barrier
Rats Brain
Drugs, Chinese Herbal
Herb-drug interaction
Herb-Drug Interactions
Male
Microdialysis
Microdialysis
Pharmacokinetic
Plant Extracts
Rats
Rats, Sprague-Dawley
Ritonavir
Ritonavir
Scutellaria baicalensis
Scutellaria baicalensis
Scutellaria baicalensis extract
Tandem Mass Spectrometry

Semantics

Type Source Name
drug DRUGBANK Ritonavir
drug DRUGBANK Scutellaria baicalensis root
disease VO Severe acute respiratory syndrome coronavirus 2
disease MESH infections
disease MESH inflammation
disease MESH viral infections
pathway REACTOME Metabolism
disease MESH herb-drug interactions
disease VO dose
disease IDO blood

Original Article

(Visited 1 times, 1 visits today)