P-glycoprotein (P-gp) affects the transport of many drugs; including puerarin and vincristine. Our previous study demonstrated that imperatorin increased the intestinal absorption of puerarin and vincristine by inhibiting P-gp-mediated drug efflux. However; the underlying mechanism was not known. The present study investigated the mechanism by which imperatorin promotes P-gp-mediated drug trans...

Recent studies showed that P-glycoprotein (P-gp) increases the portal bioavailability (FG) of loperamide by sparing its intestinal first-pass metabolism. Loperamide is a drug whose oral absorption is strongly attenuated by intestinal P-gp-mediated efflux and first-pass metabolism by cytochrome P450 3A (CYP3A). Here the effect of the interplay of P-gp and Cyp3a in modulating intestinal first-pas...

In vitro evaluation of P-glycoprotein (P-gp) inhibitory potential is now a regulatory issue during drug development, in order to predict clinical inhibition of P-gp and subsequent drug-drug interactions. Assays for this purpose, commonly based on P-gp-expressing cell lines and digoxin as a reference P-gp substrate probe, unfortunately exhibit high variability, raising thus the question of devel...

multi drug resistance(mdr) is a major problem in the treatment of cancer and hemalological malignancies. this resistance is multi factorial and is the result of decreased intra cellular drug accumulation. this is partly due to the presence of a 170kd intra membranous protein termed p-glycoprotein(p-gp) that is an energy-dependent efflux pump which has increased expression on drug-resistance cel...

The role of glucosylceramide synthase (GCS) in regulating ceramide-induced apoptosis has been widely studied. The purpose of this investigation was to evaluate the role of P-glycoprotein (P-gp) in regulating ceramide cytotoxicity by using C6-ceramide. To accomplish this, we employed HeLa cells with conditional expression of the multidrug resistance gene 1/P-gp. HeLa cells expressing P-gp (P-gp/...

P-glycoprotein (P-gp) is a membranous ATPase responsible for the multidrug resistance (MDR) phenotype. Using membrane vesicles prepared from the highly resistant cell line DC-3F/ADX we studied the influence of P-gp ATPase activity of four progesterone derivatives which specifically bind to P-gp and reverse MDR. Progesterone and desoxycorticosterone stimulate P-gp ATPase activity with, respectiv...

An empirical statistic for a class C of stationary processes is a function g which assigns to each process (Xn) ∈ C with distribution P and to each sample X1 . . . Xn of the process a real number gP (X1, . . . , Xn). We describe a condition on g which implies that the sequence (gP (X1 . . . Xn)) ∞ n=1 obeys a (universal) upcrossing inequality, that is, that the probability that this sequence fl...

Propofol is a common induction anesthetic that recently has been shown to diminish the integrity of blood brain barrier (BBB) while maintaining efflux protein expression and activity. Furthermore, Alzheimer’s disease (AD), neurodegenerative condition, compromises BBB including suppressed Efflux transporters, notably MRP-1, BCRP, P-gp, play role in clearing cytotoxic metabolites. The propofol on...

Drug resistance is a major cause of chemotherapy failure in cancer treatment. One reason is the overexpression of the drug efflux pump P-glycoprotein (P-gp), involved in multidrug resistance (MDR). In vivo pharmacokinetic analysis of P-gp transport might identify the capacity of modulation by P-gp substrate modulators, such as cyclosporin A. Therefore, P-gp function was measured in vivo with po...