TABLE 1

Quantitative evaluation of drug-drug interactions with MTX using human kidney slices

Human kidney slices were incubated with buffer containing [³H]MTX in the presence or absence of inhibitors, and K_i values were determined by nonlinear regression analysis (Fig. 3). Plasma unbound concentrations of the inhibitors (I_u) were calculated from the total plasma concentrations and unbound fractions.

Inhibitors	Clinical Concentration		K_i	R Value
Inhibitors	Total	I_u	K_i	R Value
μM
Salicylate	1100-2200^a	55-440	18.4 ± 8.6	0.040-0.25
Diclofenac	3.6^b	<0.018	26.6 ± 5.2	1.0
Indomethacin	0.84-84^a	0.084-8.4	3.11 ± 1.58	0.27-0.97
Ketoprofen	12^a	0.0096	1.85 ± 0.96	1.0
Naproxen	>217^a	0.651	14.3 ± 5.3	0.96
Phenylbutazone	162-786^a	6.3-19.0	4.87 ± 1.4	0.20-0.44
Probenecid	170^a	18.7	0.171 ± 0.8	0.009
Ciprofloxacin	7.6^c	4.5	>1000	1.0

↵ a Takeda et al. (2002).
↵ b Riess et al. (1978).
↵ c Brunton et al. (2006).