Table 2

The Ki values of various drugs that inhibit methotrexate uptake in S2 hOAT3

DrugsKi, HSA(−)Ki, HSA(+)Concentration of DrugsTotal Plasma ConcentrationUnbound FractionUnbound Plasma Concentration
HSA(−)HSA(+)
μM μM μM % μM
Salicylate102024402000200022002-a 19.62-a 431
Ibuprofen1170200048.52-a 1.00<2-a 0.485
Ketoprofen116020001.202-a 0.802-a 0.0096
Phenylbutazone34.7350507503202-b 3.902-c 12.5
Piroxicam1200200024.02-d 0.022-d 0.0048
Indomethacin5.951051020084.02-a 10.02-a 8.40
Probenecid29.8110502001702-b 11.02-c 18.7
Penicillin G97.61009.602-e 49.12-f 4.71

S2 hOAT3 was incubated with solution containing various concentrations of [3H]methotrexate in the absence or presence of various drugs. Experiments were performed in the absence or presence of 5% human serum albmin (HSA). The values for the uptake in mock were subtracted from those in S2 hOAT3. The unbound plasma concentrations were calculated from the total plasma concentrations and unbound fractions of drugs.

  • ↵2-a  Vietri et al. (2000),

  • ↵2-b  Nierenberg (1983),

  • ↵2-c  Benet et al. (1996),

  • ↵2-d  Pfizer Co., Ltd. Interview form,

  • ↵2-e  Holland et al. (1960),

  • ↵2-f  Peterson et al. (1977).