Acetaminophen-induced stimulation of MDR1 expression and activity in rat intestine and in LS 174T human intestinal cell line

In vitro and in situ evaluation of herb–drug interactions during intestinal metabolism and absorption of Baicalein

“…Therefore, compounds influencing those transporters may also affect the formation of BG and BS. For instance, APAP was shown to induce intestinal MDR1 expression in rat intestine (Ghanem et al, 2011). EC itself and its sulfates were demonstrated to be substrates of the efflux transporter MRP2 in C-2C monolayer model (Vaidyanathan and Walle, 2001).…”

Acetaminophen Changes Intestinal Epithelial Cell Membrane Properties, Subsequently Affecting Absorption Processes

“…The change in pharmacokinetics and therapeutic efficacy of these drugs, may be clinically relevant [49]. In addition, in human livers, altered MDR expression has been described in APAP consumption toxicity [50] .…”

“…We conclude that APAP pretreatment significantly (p<0.05) increases MDR1 activity, and that the efflux of APAP (parent drug) and/or its metabolites was accelerated. Ghanem et al report that APAP can induce MDR1 expression and activity in rat intestines and in the LS 174T human intestinal cell line [49]. …”

“…Efflux transporter saturation can limit the elimination of APAP itself or of subsequently administered compounds, such as drugs or nutrients [49]. Transepithelial transport of APAP has been investigated in intact rabbit intestinal tissues using Ussing chambers [51].…”

Acetaminophen Inhibits Intestinal P-Glycoprotein Transport Activity

“…We have demonstrated that the administration of repeated subtoxic, intraperitoneal doses of AP (0.2, 0.3, and 0.6 g/kg, injected in 3 consecutive days) to rats upregulated the expression and activity of P‐gp in intestine. This induction altered the pharmacokinetics of digoxin, a prototypical P‐gp substrate, decreasing its bioavailability when administered intraluminally . It has been noted that many substrates of P‐gp are also inducers of the transporter .…”