digoxin has been researched along with tariquidar* in 2 studies
2 other study(ies) available for digoxin and tariquidar
Article | Year |
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Inhibition of P-glycoprotein Gene Expression and Function Enhances Triptolide-induced Hepatotoxicity in Mice.
Triptolide (TP) is the major active principle of Tripterygium wilfordii Hook f. and very effective in treatment of autoimmune diseases. However, TP induced hepatotoxicity limited its clinical applications. Our previous study found that TP was a substrate of P-glycoprotein and its hepatobiliary clearance was markedly affected by P-gp modulation in sandwich-cultured rat hepatocytes. In this study, small interfering RNA (siRNA) and specific inhibitor tariquidar were used to investigate the impact of P-gp down regulation on TP-induced hepatotoxicity. The results showed that when the function of P-gp was inhibited by mdr1a-1 siRNA or tariquidar, the systemic and hepatic exposures of TP were significantly increased. The aggravated hepatotoxicity was evidenced with the remarkably lifted levels of serum biomarkers (ALT and AST) and pathological changes in liver. The other toxicological indicators (MDA, SOD and Bcl-2/Bax) were also significantly changed by P-gp inhibition. The data analysis showed that the increase of TP exposure in mice was quantitatively correlated to the enhanced hepatotoxicity, and the hepatic exposure was more relevant to the toxicity. P-gp mediated clearance played a significant role in TP detoxification. The risk of herb-drug interaction likely occurs when TP is concomitant with P-gp inhibitors or substrates in clinic. Topics: Alanine Transaminase; Animals; Apoptosis Regulatory Proteins; Aspartate Aminotransferases; ATP Binding Cassette Transporter, Subfamily B; Cell Line, Tumor; Chemical and Drug Induced Liver Injury; Digoxin; Diterpenes; Epoxy Compounds; Gene Knockdown Techniques; Immunologic Factors; Male; Mice, Inbred BALB C; Molecular Docking Simulation; Oxidative Stress; Phenanthrenes; Protein Binding; Quinolines; RNA, Small Interfering | 2015 |
Potential role for human P-glycoprotein in the transport of lacosamide.
Antiepileptic drugs (AEDs) do not effectively treat 30-40% of patients with epilepsy. Export of AEDs by P-glycoprotein (Pgp, ABCB1, or MDR1), which is overexpressed in the blood-brain barrier in drug-resistant patients, may be a mechanism for resistance to AEDs. For most recently approved AEDs, whether they are transported by Pgp is unknown. We investigated whether a new AED, lacosamide (LCM), is a substrate of human Pgp.. LLC-PK1 and MDCKII cells transfected with the human MDR1 gene were used to determine the substrate status of LCM in concentration equilibrium transport assays (CETAs). An equal concentration of drug was initially loaded in both the apical and basal chambers, and the concentration in both chambers was measured up to 4 h. The experiments were repeated in the presence of the Pgp inhibitors verapamil and tariquidar. Caco-2 assays were used to determine the intrinsic permeability and efflux ratio of LCM as well as its potential to inhibit digoxin, a Pgp substrate.. Lacosamide was transported by MDR1-transfected cells from basolateral to apical sides. The efflux of LCM could be completely blocked by verapamil or tariquidar. In Caco-2 assays, LCM showed high permeability without a significant efflux ratio; it did not inhibit digoxin, a Pgp substrate.. Although LCM is a substrate of Pgp in CETA, Caco-2 data demonstrated that passive diffusion should play a major role in the overall disposition of LCM. The critical role of Pgp should be addressed in vivo. Topics: Acetamides; Animals; Anticonvulsants; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Transport; Calcium Channel Blockers; Cell Line; Digoxin; Dogs; Dose-Response Relationship, Drug; Enzyme Inhibitors; Gene Expression Regulation; Humans; Lacosamide; Quinolines; Rhodamine 123; RNA, Messenger; Swine; Time Factors; Transfection; Tritium; Verapamil | 2013 |