Table 1

The effects of various NSAIDs on methotrexate uptake mediated by hOAT1, hOAT3, and hOAT4

DrugshOAT1hOAT3hOAT4
Salicylate84.7  ± 7.951-165 41.5  ± 2.901-150 94.8  ± 8.53
Ibuprofen47.0  ± 3.051-150 64.0  ± 3.301-160 67.8  ± 5.231-160
Ketoprofen53.4  ± 5.431-150 45.2  ± 3.451-150 81.0  ± 1.781-165
Phenylbutazone30.0  ± 1.131-150 31.3  ± 2.431-150 55.7  ± 7.201-150
Piroxicam40.9  ± 10.71-150 56.2  ± 3.821-150 62.0  ± 8.341-160
Indomethacin60.6  ± 7.261-150 38.5  ± 3.111-150 60.9  ± 5.741-160
Probenecid52.1  ± 4.291-150 30.2  ± 4.321-150 81.6  ± 6.261-165
Penicillin G102.3  ± 6.1827.8  ± 2.561-150 79.7  ± 4.881-165

S2 hOAT1, S2 hOAT3, and S2 hOAT4 were incubated with solution containing 1 μM [3H]methotrexate in the absence or presence of various NSAID drugs. The concentrations of NSAIDs used were 1 mM except 0.5 mM for indomethacin. The values for the uptake in mock were subtracted from those in S2 hOAT1, S2 hOAT3, and S2hOAT4. Each value represents the mean ± S.E. of four determinations from one typical experiment of the two separate experiments.

  • 1-150P < 0.001,

  • 1-160P < 0.01, and

  • 1-165P < 0.05 versus control.