Acetaminophen (AP) inhibits intestinal P-glycoprotein (P-gp) activity in vitro and in vivo

NOVAK A; DELLI CARPINI G; RUIZ ML; LUQUITA MG; RUBIO M; MOTTINO AD; GHANEM CI

Boston

Congreso; Experimental Biology 2013; 2013

AP induces long-term regulation of expression of intestinal P-gp. Whether it can acutely modulate P-gp activity is unknown. Aims: To study the effect of AP on rat intestinal P-gp activity in vivo and in vitro. M&M: In vitro. Intestinal everted sacs were filled with rhodamine 123 (serosal), a tipical P-gp substrate, (R123; 4.5; 9; 12; 18 or 36 μM) and incubated in KH buffer (mucosal) alone or with AP (100 μM), and secretion of R123 was assessed along a 40-min period. Serosal-mucosal transport of AP was studied in a similar fashion, in the presence/absence of Psc 833 (10 μM), a specific inhibitor of P-gp. Transport of AP (10 μM) was also evaluated in P-gp knock down HepG2 cells. In vivo. Intestinal absorption of digoxin (Dig, 25.6 nmol/kg) was studied by portal vein sampling (30-min period) in the presence or absence of AP (100 μM). Results: R123 transport adjusted well to a sigmoideal curve. Its Vmax was decreased by AP (P