P-glycoprotein expression is increased by St. John's Wort: Consequences for medication interactions

• Nerea Angel

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Although Rims St. John's Wort (SJW) is frequently used to treat depression, there are worries that it may 
interfere with other medications. Indinavir and cyclosporin trough plasma concentrations have 
significantly decreased when co-administered with SJW [1, 2]. The most likely mechanism of interaction 
has been identified as induction of cytochrome P450 3A4 (CYP3A4). The size of the interaction observed 
in clinical practice, however, is more than what in vitro research indicated, indicating the possibility of 
further interaction pathways. Since cyclosporin and indinavir are substrates for both CYP3A4 and the 
multidrug transporter P-glycoprotein, we postulated that SJW's modification of P-glycoprotein expression 
and activity could lead to the emergence of potentially dangerous drug-drug interactions. 

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