A pharmacokinetic drug –drug interaction study between rosuvastatin and emvododstat, a potent anti‐SARS‐CoV‐2 (COVID‐19) DHODH (dihydroorotate dehydrogenase) inhibitor

Emvododstat (PTC299) was found to be a potent inhibitor of immunomodulatory and inflammation-related processes by the inhibition of dihydroorotate dehydrogenase (DHODH) to reduce SARS-CoV-2 replication. This drug interaction study was performed to determine whether emvododstat was an inhibitor of breast cancer resistance protein (BCRP) transporters in humans using a BCRP substrate, rosuvastatin. Drug interaction studies showed that emvododstat was an in vitro inhibitor of BCRP transporters.  The 90% CIs for AUC and Cmax indicated no apparent PK interaction between the BCRP substrate rosuvastatin and emvododstat. Furthermore, the study indicates that in general, emvododstat does not appear to inhibit BCRP transport and that one should not anticipate a PK interaction or need to adjust the dose with other BCRP substrate drugs. AbstractA therapeutic agent that targets both viral replication and the hyper-reactive immune response would offer a highly desirable treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) management. Emvododstat (PTC299) was found to be a potent inhibitor of immunomodulatory and inflammation-related processes by the inhibition of dihydroorotate dehydrogenase (DHODH) to reduce SARS-CoV-2 replication. DHODH is the rate-limiting enzyme of the de novo pyrimidine nucleotide biosynthesis pathway. This drug interaction study was performed to determine whether emvododstat was an inhibitor of breast cancer resistance protein (BCRP) t...
Source: Pharmacology Research and Perspectives - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL ARTICLE Source Type: research