Potential Alteration of Rifampicin's Bioavailability by Phyllanthus niruri Supplementation in Tuberculosis Therapy.

Rifampicin is essential for treating TB. The high incidence of resistance to this drug requires efforts to increase the effectiveness of TB therapy. Immunomodulator supplementation is one effort to overcome this problem. Phyllanthus niruri has an immunomodulating effect, which has been proven to influence the clinical improvement of the immunological profile. However, the effect of this plant on rifampicin's bioavailability should be reviewed to determine potential changes that may affect its antibacterial performance. Several stud-ies have shown an increase in the bioavailability of rifampicin when administered with extracts and active isolates of Carum carvi, Cuminum cyminum, Piper nigrum, and Moringa oleifera through inhibition of the P-gp efflux function in the absorption phase. On the other hand, the decrease occurred in coadministration with Garcinia cola, which activated PXR action and subsequently changed P-gp regulation. Administration of Al-lium sativum and Zingiber officinale extracts did not show significant alteration in bioavailability due to the stimulation of several mechanisms with opposite outputs by each secondary metabolite. In the case of P. niruri supplementation, the potential for a rise in bioavailability could occur due to synergistic effects inhibiting the performance of P-gp, AADAC, and OATP1B. However, the stimulation of PXR and PPARα may reduce or eliminate these effects. Finally, considering that there are so many specific secondary metabolites in P. niruri whose effects on the performance of these functional proteins have not been exposed, in vivo studies are needed to confirm the interactions within complex biological systems.