Evodiamine decreased the systemic exposure of pravastatin in non-alcoholic steatohepatitis rats due to the up-regulation of hepatic OATPs

Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients

“…The dysregulation in drug and enzyme activities that can occur in NASH may also precipitate the onset of drug–drug interactions between these different drugs and might result in unexpected ADRs associated with these drugs, even when used at pharmaceutical doses. Recently, several preclinical studies also demonstrated drug–herb interactions in preclinical models of NASH 612 , 613 , 614 , 615 . The botanical natural product silymarin for example can be used for the treatment of NASH disease and contains flavonolignans that are both substrates and inhibitors of the OATP hepatic transporters 612 , 613 .…”

“…Preclinical studies showed that the use of silymarin in a NASH model of rats caused an additive increase in pitavastatin plasma concentrations associated to a decrease of its biliary excretion, due to the silymarin–pitavastatin interaction at the OATP level, whose protein expression is also affected by the disease 612 , 613 . Another study demonstrated that evodiamine, a quinolone alkaloid extracted from a traditional Chinese herb that may be used in NASH for anti-obesity, anti-inflammatory, and anti-cardiovascular properties, affected the pharmacokinetics of pravastatin only in NASH rats by enhancing the OATP hepatic distribution of the drug, probably previously decreased by the disease 615 . Finally, a rodent study showed that the risk of hepatotoxicity related to coadministration of simvastatin and Gardenia jasminoides J. Ellis (frequently used together in patients with multi-morbidity, such as stroke rehabilitation patients with NASH) was lowered in the NASH group compared to the control group that might be partially explained by the upregulation of P-gp in the NASH animals 614 .…”

The role of organic anion transport protein 1a4 in drug delivery and diseases: a review

“…Perinatal exposure to polybrominated diphenyl ethers (PBDEs) resulted in increased expression of the hepatic efflux transporters Mdr1 (multidrug resistance), Mrp2 (multidrug resistanceassociated protein) and Mrp3, and the influx transporter Oatp1a4 mRNA (Szabo et al, 2009). Patients with nonalcoholic steatohepatitis (NASH) may ingest both Pravastatin and herbs containing Evodiamine, which upregulates the expression of Oatp1a1, Oatp1a4, and Oatp1b2 decreasing systemic exposure to pravastatin (Liang et al, 2022). The regulation of Oatp1a4 by some natural products or traditional drugs has also been reported.…”