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 | Ki | R 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 |