Table 2.

K_{i ,app} with regard to pyrimethamine C _av, f _PYR, and in vitro K_i of test compounds

Compound	Clinical data		In vitro Ki (μM)
	Ki ,app, μM	f PYR	OCT2	MATE1	MATE2‐K
Metformin	1.05 ± 0.39 (0.137)	0.766 ± 0.103	37.9 ± 5.6	0.154 ± 0.029	0.0941 ± 0.016
N 1‐methyladenosine	1.94 ± 0.96 (0.252)	0.792 ± 0.188	0.466 ± 0.043	ND	0.0680 ± 0.015
Creatinine	0.0914 ± 0.0661 (0.0119)	0.260 ± 0.026	1.57 ± 0.24	ND	ND
N 1‐methylnicotinamide a	1.37 ± 0.63 (0.178)	0.863 ± 0.157	41.2 ± 9.1	0.125 ± 0.026	0.0821 ± 0.018

K_{i ,app} and f _PYR were determined by iterative nonlinear regression analysis using renal clerance ratio, and average pyrimethamine concentrations, as described in the Methods. In vitro K_i were determined by iterative nonlinear regression analysis using the data shown in Figure 5 . Number in the parenthesis represents the K_{i ,app} corrected by the unbound fraction of pyrimethamine in the plasma (0.13). Each parameter represents the fitted parameter with computer calculated SD. K _i was calculated from IC₅₀, assuming IC₅₀ approximates K _i when substrate concentration is lower than the K_m.

C_av, mean plasma concentration; f _PYR, fraction sensitive to inhibition by pyrimethamine; K_i, inhibition constant; K _i,app, apparent inhibition constant of pyrimethamine as the total concentration; ND, not determined.

^aCL_r calculated from time zero to 12 hours was used in the analysis.