Induction Of Cyp3a4 Activity In The Intestinal Wall

Human studies have identified CYP3A4 and 2C19 induction effects for standard SJW extracts (e.g. LI 160), but no effects on CYP1A2, CYP2C9 or CYP2D6 (Durr et al 2000, Jiang et al 2004, Wang et al 2001, 2004a).

Human studies have failed to identify significant CYP3A4, 2D6, 2C9, 1A2 or 2C19 induction for low-hyperforin SJW extracts, such as ZE 117, using the appropriate probe drugs (Arold et al 2005, Madabushi et al 2006, Mueller et al 2004).

Hyperforin is a potent ligand for the pregnane X receptor, an orphan nuclear receptor that regulates expression of the CYP3A4 mono-oxygenase (Moore et al 2000). Although it is considered the chief constituent responsible for the pharmacokinetic interactions reported, there are other, less potent constituents in SJW which also modulate cytochrome enzymes (Obach 2000).

Results from an open label clinical study suggest that the effects of standard SJW (LI 160) on CYP3A4 enzymes may be biphasic, where the initial dose leads to a minor inhibition, followed by significant induction during long-term use (Rengelshausen et al 2005).

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