Physiologically based pharmacokinetic modeling for dose optimization of quinine-phenobarbital coadministration in patients with cerebral malaria.

ABSTRACT: Patients with cerebral malaria with polymorphic Cytochrome P450 2C19 (CYP2C19) genotypes who receive concurrent treatment with quinine are at risk of inadequate or toxic therapeutic drug concentrations due to metabolic drug interactions. The study aimed to predict the potential dose regimens of quinine when coadministered with phenobarbital in adult patients with cerebral malaria and complications (e.g., lactic acidosis and acute renal failure) and concurrent with seizures and acute renal failure who carry wild-type and polymorphic CYP2C19. The whole-body physiologically based pharmacokinetic (PBPK) models for quinine, phenobarbital, and quinine-phenobarbital coadministration were constructed based on the previously published information using Simbiology®. Four published articles were used

SUBMITTER: Sae-Heng T 

PROVIDER: S-EPMC8752110 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature