Overexpression of P-glycoprotein, MRP2, and CYP3A4 impairs intestinal absorption of octreotide in rats with portal hypertension

Table 1 Effect of P-gp and MRP2 inhibition on OCT transport by Caco-2 cells

Inhibition		OCT 1 μM		OCT 10 μM		OCT 50 μM
Inhibition		A-B	B-A	A-B	B-A	A-B	B-A
MRP2	P_app(× 10⁻⁶ cm/s)	0.007 ± 0.001	0.006 ± 0.001	0.149 ± 0.016^a	0.31 ± 0.025^b	0.353 ± 0.032	1.13 ± 0.097
MRP2	PDR(B-A/A-B)	0.9		2.1		3.2
P-gp	P_app(× 10⁻⁶ cm/s)	0.010 ± 0.001	0.012 ± 0.002	0.168 ± 0.018^a	0.297 ± 0.024^b	1.192 ± 0.072	1.040 ± 0.084
P-gp	PDR(B-A/A-B)	1.2		1.8		0.9
MRP2 and P-gp	P_app(× 10⁻⁶ cm/s)	0.022 ± 0.002	0.006 ± 0.001	0.368 ± 0.055^a,c	0.193 ± 0.021^b,c	1.725 ± 0.138	0.981 ± 0.082
MRP2 and P-gp	PDR(B-A/A-B)	0.3		0.5		0.6
Control	P_app(× 10⁻⁶ cm/s)	0.005 ± 0.001	0.021 ± 0.003	0.127 ± 0.015	0.565 ± 0.073^c	0.23 ± 0.021	1.334 ± 0.160
Control	PDR(B-A/A-B)	4.1		4.4		5.8

Results are expressed as mean ± SD; n = 4 per treatment
A-B, Apical-to-Basolateral; B-A, Basolateral-to-Apical
P_app, permeability coefficient; PDR, permeability direction rate
^aIndicates p < 0.05 for: P_app (A to B) of MRP2 and P-gp inhibition versus P_app (A to B) of MRP2 or P-gp inhibition; P_app (A to B) of P-gp inhibition versus control; and P_app (A to B) of MRP2 inhibition versus Control
^bIndicates p < 0.05 for P_app (B to A) versus P_app (A to B) upon inhibition of MRP2 or P-gp and combined inhibition of MRP2 and P-gp
^cIndicates p < 0.01 for: P_app (A to B) of MRP2 and P-gp inhibition versus Control; P_app (B to A) of MRP2 and P-gp inhibition versus control; and P_app (B to A) control versus P_app (A to B) control (control = 10 μM OCT)

ISSN: 1471-230X