P-glycoprotein inducers

P-Glycoprotein Substrates P-Glycoprotein Inhibitors P-Glycoprotein Inducers... 

P-glycoprotein (P-gp) works as a transporter at the intestinal mucosa pumping drugs out into the lumen. Absorption of P-gp substrates, such as digoxin, cyclosporine, etc., can be increased by inhibitors of P-gp and reduced by inducers. 

Zhang, W. et al.. Impact of curcnmin-induced changes in P-glycoprotein and CYP3A expression on the pharmacokinetics of peroral cehprolol and midazolam in rats. Drug Metab. Dispos., 35, 110, 2007. 

P-glycoprotein, a plasma membrane transport protein, is present in the gut, brain, liver, and kidneys 42 This protein provides a biologic barrier by eliminating toxic substances and xenobiotics that may accumulate in these organs. P-glycoprotein plays an important role in the absorption and distribution of many medications. Medications that are CYP3A4 substrates, inhibitors, or inducers are also often affected by P-glycoprotein therefore, the potential for even more DDIs exists in transplant recipients.42... 

A. H., Meijer, D. K., Heterologous expression of various P-glycoproteins in polarized epithelial cells induces directional transport of small (type 1) and bulky (type 2) cationic drugs, J. Pharmacol. Exp. Ther. 1998, 286, 321— 327. 

Ambudkar, S. V., Correlation between steady-state ATP hydrolysis and vanadate-induced ADP trapping in human P-glycoprotein. Evidence for ADP release as the rate-limiting step in the catalytic cycle and its modulation by substrates, J. Biol. Chem. 2001, 276, 8657-8664. 

Loo, T.W., Bartlett, M.C. and Clarke, D.M. (2003) Substrate-induced conformational changes in the transmembrane segments of human P-glycoprotein. Journal of Biological Chemistry, 278, 13603-13606. 

G.R. Lankas, L.D. Wise, M.E. Cartwright, T. Pippert, and D.R. Umbenhauer. Placental P-glycoprotein deficiency enhances susceptibility to chemically induced birth defects in mice. Reprod Toxicol. 12 457-463 (1998). 

O. van Tellingen, T. Buckle, J.W. Jonker, M.A. van der Valk, and J.H. Beijnen. P-glycoprotein and Mrpl collectively protect the bone marrow from vincristine-induced toxicity in vivo. Br J Cancer. 89 1776-1782 (2003). 

Nwaozuzu OM, Sellers LA, Barrand MA (2003) Signalhng pathways influencing basal and H(2)0(2)-induced P-glycoprotein expression in endothelial cells derived from the blood-brain barrier. J Neurochem 87 1043-1051... 

Perloff MD, von Moltke LL, Greenblatt DJ (2004) Ritonavir and dexamethasone induce expression of CYP3A and P-glycoprotein in rats. Xenobiotica 34 133-150... 

D. Durr, B. Stieger, G. A. Kullak-Ublick, K. M. Rentsch, H. C. Steinert, P. J. Meier, and K. Fattinger. St John s Wort induces intestinal P-glycoprotein/MDRl and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 68 598-604 (2000). 

Bezombes, C., Maestre, N., Laurent, G., Levade, T., Bettaieb, A., and Jaffrezou, J. P., 1998, Restoration of TNF-a-induced ceramide generation and apoptosis in resistant human leukemia KGla cells by the P-glycoprotein blocker PSC833. FASEB J. 12 101-109. 

Absorption - Absorption of tipranavir in humans is limited. Tipranavir is a P-glycoprotein (P-gp) substrate, a weak P-gp inhibitor, and appears to be a potent P-gp inducer as well. Steady state is attained in most subjects after 7 to 10 days of dosing. 

Sakata K, Kwok TT, Murphy BJ, Laderoute KR, Gordon GR, Sutherland RM (1991) Hypoxia-induced drug resistance comparison to P-glycoprotein-assodated drug resistance. Br J Cancer 64 809-814... 

TABLE 5.1 Select P-glycoprotein Substrates, Inhibitors, and Inducers... 

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