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...

OBJECTIVES To evaluate the role of P-glycoprotein (P-gp) and multidrug-resistant-protein 1 (MRP1) on raltegravir intracellular drug disposition in CD4+ T cells, investigate the effect of HIV-1 infection on P-gp expression and correlate HIV-1 viraemia with P-gp activity in primary CD4+ T cell subsets. METHODS The cellular accumulation ratio of [(3)H]raltegravir was quantified in CD4+ T cell li...

ATP-binding cassette transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) have been shown to work in concert to restrict brain penetration of several tyrosine kinase inhibitors. It has been reported that P-gp is dominant in limiting transport of many dual P-gp/BCRP substrates across the blood-brain barrier (BBB). This study investigated the influence of P-gp and BCRP o...

We first report on computations made using the GP/PARI package that show that the error term Δ(x) in the divisor problem is = M (x, 4)+ O∗(0.35x1/4 log x) when x ranges [1 081 080, 1010], where M (x, 4) is a smooth approximation. The remaining part (and in fact most) of the paper is devoted to showing that |Δ(x)| ≤ 0.397x1/2 when x ≥ 5 560 and that |Δ(x)| ≤ 0.764x1/3 log x when x ≥ 9 995. Sever...

The purpose of this study was to evaluate the impact of intestinal efflux transporters on the in vivo oral absorption process. Three model drugs-fexofenadine (FEX), sulfasalazine (SASP), and topotecan (TPT)-were selected as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and P-gp and BCRP substrates, respectively. The drugs were orally administered to portal vein-cannulated rats...

BACKGROUND Despite widespread use of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors for percutaneous coronary interventions (PCI) of bypass grafts, data supporting this strategy are lacking. METHODS AND RESULTS A pooled analysis of 5 randomized intravenous GP IIb/IIIa inhibitor trials (EPIC, EPILOG, EPISTENT, IMPACT II, and PURSUIT) was performed, and outcomes of graft interventions ...

Using in vitro data, we previously built Catalyst 3-dimensional quantitative structure activity relationship (3D-QSAR) models that qualitatively rank and predict IC(50) values for P-glycoprotein (P-gp) inhibitors. These models were derived and tested with data for inhibition of digoxin transport, calcein accumulation, vinblastine accumulation, and vinblastine binding. In the present study, 16 i...

The purpose of this study was to evaluate the impact of intestinal efflux transporters on the in vivo oral absorption process. Three model drugs—fexofenadine (FEX), sulfasalazine (SASP), and topotecan (TPT)—were selected as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and P-gp and BCRP substrates, respectively. The drugs were orally administered to portal vein– cannulated rat...

P-glycoprotein (P-gp), a drug efflux transporter, affects the pharmacokinetics of a wide range of substrate drugs. Our previous study clearly revealed that intestinal P-gp expression levels were decreased via an inducible nitric oxide synthase (iNOS)-mediated mechanism in the early phases of diabetes. Here, we focused on changes in ileal P-gp expression and the influences of NOS on the P-gp exp...

The delivery method of [continuous (CONT) vs. every other day or intermittent (INT)] a glucogenic precursor (GP) which was contained glycerin (500 g/kg), mono-propylene glycol (250 g/kg), calcium propionate (150 g/kg), niacin (1 g/kg) and sulfate-Co (350 mg/kg) on performance, selected blood metabolites and liver enzymes were evaluated. Twenty-four multiparous Holstein fresh cows were ...