TABLE 1

IC₅₀ values for hOAT3 in MTX uptake and plasmatic concentrations of proton pump inhibitors according to CYP2C19 genetic polymorphism and plasma unbound fraction

PPI dosage and maximal total PPI concentration in the systemic circulation (C_max) were obtained from the indicated references. [I] = (C_max total) * (% plasma unbound fraction)/100].

Compounds	Uptake MTX IC₅₀ hOAT3	Dose	Genotype CYP2C19	C_max Observed in Humans	[I]	[I]/IC₅₀	References
	µM	mg		µM
Omeprazole	6.80 ± 1.16	20	EM	1.6 ± 1.0	0.05 ± 0.03	0,007	(Regardh et al., 1990; Yasuda et al., 1995)
Omeprazole	6.80 ± 1.16	20	PM	3.1 ± 0.9	0.10 ± 0.03	0,015	(Regardh et al., 1990; Yasuda et al., 1995)
Lansoprazole	1.14 ± 0.26	30	EM	2.44 ± 0.7	0.07 ± 0.02	0,061	(Ieiri et al., 2001; Freston et al., 2003)
Lansoprazole	1.14 ± 0.26	30	PM	4.9 ± 0.08	0.15 ± 0.02	0,132	(Ieiri et al., 2001; Freston et al., 2003)
Pantoprazole	4.45 ± 1.62	40	EM	5.4 ± 1.4	0.11 ± 0.03	0,025	(Regardh et al., 1990; Pue et al., 1993)
Pantoprazole	4.45 ± 1.62	40	PM	11.5 ± 7.80	0.23 ± 0.16	0,052	(Regardh et al., 1990; Pue et al., 1993)

PM, poor metabolizer phenotype; EM, extensive metabolizer phenotype. [I], unbound inhibitor concentration.