TABLE 1

IC₅₀ values of various NSAIDs for MRP2- and MRP4-mediated MTX transport

[³H]MTX uptake was measured by subtracting the background (AMP) from the ATP-dependent uptake. Each value represents the mean ± S.E. of data obtained from three separate experiments, each performed in triplicate, calculated by nonlinear regression analysis of the data from Figs. 4 and 5.

NSAID	MRP2	MRP4
	μM
Salicylate	1760 ± 30	1500 ± 20
Piroxicam	257 ± 2	216 ± 2
Ibuprofen	930 ± 20	26.3 ± 0.3
Naproxen	609 ± 7	42.3 ± 0.3
Sulindac	38 ± 1	2.11 ± 0.02
Tolmetin	494 ± 5	20.5 ± 0.3
Etodolac	480 ± 2^a	120 ± 1
Diclofenac	97 ± 1	0.006 ± 0.001 (H)
		326 ± 6 (L)
Indomethacin	0.06 ± 0.01 (H)	6.1 ± 0.1
	46 ± 1 (L)
Ketoprofen	1.4 ± 0.1 (H)	11.9 ± 0.1
	470 ± 20 (L)
Celecoxib	100 ± 2	35 ± 1^b
Phenylbutazone	605 ± 4^b	130 ± 2

↵ a Dose-inhibition curve with a slope factor > 1. High (H)- and low (L)-affinity IC₅₀ determined according to a two-site competition model.
↵ b Stimulation of uptake at low concentrations.