In the present investigation 16 phytoconstituents, which are active moieties found in several medicinal herbs, have been evaluated for their P-glycoprotein (P-gp) stimulation/inhibition profiles using a P-gp-dependent ATPase assay in rat jejunal membrane (in vitro). Acteoside, agnuside, catechin, chlorogenic acid, picroside -II and santonin showed an inhibitory effect. Negundoside, picroside -I and oleanolic acid caused a stimulatory effect. Andrographolide, apocyanin, berberine, glycyrrhizin, magniferin and piperine produced a biphasic response (stimulation at low concentration and inhibition at high concentration). The results suggested that a possible interaction of these phytoconstituents at the level of P-gp, could be an important parameter in determining their role in several key pharmacodynamic events.
This study deals with the pharmacokinetic interaction of selected anti-TB drugs with a natural product (CC-1a) derived from caraway ( Carum carvi, L.) seed. CC-1a, chemically standardized butanolic fraction, enhanced the plasma levels of rifampicin, pyrazinamide, and isoniazid in Wistar rat, resulting in increased bioavailability indices (Cmax and AUC) of the drugs. Moreover, a 40% reduced dose regimen of these drugs, which additionally contained CC-1a, was equivalent in terms of Cmax and AUC to a normal dose regimen. A permeation-enhancing property of CC-1a across small intestinal absorptive surface was found to be a contributing factor in its bioavailability enhancing profile.
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