Up-regulation of the membrane-bound efflux pump P-glycoprotein (P-gp) is associated with the phenomenon of multidrug-resistance in pathogenic organisms, including protozoan parasites. In addition, P-gp plays a role in normal physiological processes, however our understanding of these P-gp functions remains limited. In this study we investigated the effects of the P-gp inhibitor GF120918 in Toxo...

OBJECTIVES To investigate whether P-glycoprotein (P-gp) and multidrug resistance proteins (MRPs), which limit the bioavailability of HIV protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs), modulate the anti-HIV activity of NRTIs, non-NRTIs and PIs in vitro. DESIGN We used primary cultures of major HIV target cells: human monocyte-derived macrophages (MDMs) and l...

BACKGROUND AND OBJECTIVES Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor under clinical investigation in solid tumours. This study evaluated the influence of P-glycoprotein (P-gp) inhibition (single-dose rifampicin) and simultaneous cytochrome P450 3A4 (CYP3A4)/P-gp induction (multiple-dose rifampicin) on lenvatinib pharmacokinetics. METHODS This Phase I, single-centre, single...

BACKGROUND P-glycoprotein (P-gp) is an ATP-dependent membrane transporter that plays a pivotal role in eliminating xenobiotics by active extrusion of xenobiotics from the cell. Multidrug resistance (MDR) is highly associated with the over-expression of P-gp by cells, resulting in increased efflux of chemotherapeutical agents and reduction of intracellular drug accumulation. It is of clinical im...

BACKGROUND The ABC transporter P-glycoprotein (P-gp) is recognized as a site for drug-drug interactions and provides a mechanistic explanation for clinically relevant pharmacokinetic interactions with digoxin. The question of whether several P-gp inhibitors may have additive effects has not yet been addressed. METHODS We evaluated the effects on serum concentrations of digoxin (S-digoxin) in ...

Labisia pumila (Kacip Fatimah) is a popular herb in Malaysia that has been traditionally used in a number of women's health applications such as to improve libido, relieve postmenopausal symptoms, and to facilitate or hasten delivery in childbirth. In addition, the constituents of this plant have been reported to possess anticancer, antioxidant, and anti-inflammatory properties. Clinical studie...

P-glycoprotein (P-gp) is an ATP-dependent transport protein that is selectively expressed at entry points of xenobiotics where, acting as an efflux pump, it prevents their entering sensitive organs. The protein also plays a key role in the absorption and blood-brain barrier penetration of many drugs, while its overexpression in cancer cells has been linked to multidrug resistance in tumors. The...

The effect of hydrophobic extracts of human and rat urine on in-vitro P-glycoprotein (P-gp) function was examined, in terms of intra-, inter-individual variations, and physiological states. Six urine samples out of 7, obtained from one male subject on different days, suppressed P-gp function with different potencies. Similarly, 11 samples out of 15 different individuals (8 males and 7 females) ...

In the quest to explore the reason for the low and variable bioavailability of lumefantrine, we investigated the possible role of P-glycoprotein (P-gp) in lumefantrine intestinal absorption. An in situ single-pass intestinal perfusion study in rats with the P-gp inhibitor verapamil or quinidine and an ATPase assay with human P-gp membranes indicated that lumefantrine is a substrate of P-gp whic...