Intestinal drug efflux: formulation and food effects

Safety evaluation of naringenin upon experimental exposure on rat gastrointestinal epithelium for novel optimal drug delivery

“…It has been demonstrated that a number of excipients, such as polyethylene glycols (PEGs), non-ionic surfactants, fatty acids and bile salts (Nerurkar et al, 1996(Nerurkar et al, , 1997Lo & Huang, 2000;Arima et al, 2001;Johnson et al, 2002;Hugger et al, 2002aHugger et al, ,2002bHugger et al, , 2003 could inhibit the function of P-gp, thereby increasing the absorption of P-gp substrate drugs (Wagner et al, 2001).…”

Instrumented In Vitro Approaches to Assess Epithelial Permeability of Drugs from Pharmaceutical Formulations

“…Wu et al [33] suspected that concomitant intake of highfat meals with drugs is inhibiting intestinal influx and efflux drug transporters and thus may lead to decreased bioavailability of BCS class III compounds; however, due to increased solubility in the intestinal lumen after fatty meals, BCS class II compounds may show an increased postprandial bioavailability. Inhibition of intestinal efflux transporters may also be mediated by flavonols in grapefruit and orange juice, as stated in a review by Wagner et al [14]. Ingels et al [34] reported that the application of FaSSIF in Caco-2 permeability assessment does not affect the permeability of passively permeating compounds.…”

“…[5,[14][15][16][17][18][19][20]. Many authors report increased drug fluxes from apical to basolateral and decreased fluxes in the adverse direction in presence of polyethoxylated surface active excipients such as Tween 80, vitamin E TPGS, pluronic block polymers, and Cremophor EL.…”

“…Effects of concomitant intake of food with drugs on disintegration [26] and dissolution [14,[27][28][29][30][31] of oral solid dosage forms have been extensively described in the literature. For dissolution testing, the development of biorelevant dissolution media by Galia et al [1], simulating intestinal fluid in fed (FeSSIF) and fasted state (FaSSIF), led to a generally accepted in vitro method to forecast food effects on dissolution.…”

“…For dissolution testing, the development of biorelevant dissolution media by Galia et al [1], simulating intestinal fluid in fed (FeSSIF) and fasted state (FaSSIF), led to a generally accepted in vitro method to forecast food effects on dissolution. Nevertheless, effects of food components on absorption processes are getting more and more into the focus of research [14,32]. Wu et al [33] suspected that concomitant intake of highfat meals with drugs is inhibiting intestinal influx and efflux drug transporters and thus may lead to decreased bioavailability of BCS class III compounds; however, due to increased solubility in the intestinal lumen after fatty meals, BCS class II compounds may show an increased postprandial bioavailability.…”