Schisandrol A and Schisandrol B from Schisandra chinensis: Drug Metabolism, Transporter Interactions, and Herb-Drug Interaction Potential.

Schisandrol A (Sch A) and Schisandrol B (Sch B) are structurally related dibenzocyclooctadiene lignans from Schisandra chinensis, but their drug-metabolism and interaction profiles are not interchangeable. This review critically evaluates their absorption, distribution, metabolism, transporter interactions, nuclear-receptor regulation, and herb-drug interaction potential, with particular emphasis on the distinction between purified compounds and multi-lignan botanical preparations. Oral exposure is strongly formulation dependent. In rats, purified Sch B shows substantially lower absolute bioavailability than Sch B administered within S. chinensis extract, whereas available Sch A studies likewise indicate considerable effects of formulation on systemic exposure. CYP3A4 is a major oxidative pathway for both compounds, although Sch B shows a more prominent interaction liability through reversible and time-dependent CYP3A inhibition. Both lignans can modulate P-glycoprotein function, but available transport studies do not support their blanket classification as conventional P-glycoprotein substrates. Sch B additionally activates pregnane X receptor signaling, creating a mechanistic distinction between acute enzyme inhibition and potential induction during repeated exposure. Animal drug-interaction studies and physiologically based pharmacokinetic models support interaction potential, while clinical evidence is strongest for multi-lignan Wuzhi preparations that alter tacrolimus disposition. Direct human evidence remains limited, particularly for purified Sch B and repeated-dose compound-specific interaction studies. Pharmacological findings therefore need to be interpreted in relation to experimentally achieved exposure rather than assumed therapeutic equivalence. Future work should prioritize well-defined human pharmacokinetics, quantitative inhibition-induction assessment, formulation-dependent exposure, and long-term safety to establish the clinical relevance of Sch A and Sch B.