TABLE 3

Quantitative evaluation of drug-drug interactions between MTX and NSAIDs via MRP4

Inhibitory effect of NSAIDs on MRP4-mediated transport of MTX was examined, and Ki values were determined by nonlinear regression analysis. All Ki values represent the mean ± S.D. Plasma unbound concentrations of the inhibitors (Iu) were calculated from the total plasma concentrations and unbound fractions.

Inhibitors Clinical Concentration KiR Value
Total Iu
μM
Salicylate 1100-2200a 55-440 218 0.33-0.80
Diclofenac 3.6b <0.018 >100 1.0
Indomethacin 0.84-84a 0.084-8.4 2.95 0.26-0.97
Ibuprofen 48.5a <0.485 73.3 1.0
Ketoprofen 12a 0.0096 23.3 1.0
Naproxen >217a 0.651 75.3 0.99
Phenylbutazone 162-786a 6.3-19.0 354 0.95-0.98
  • a Takeda et al. (2002).

  • b Riess et al. (1978).