TABLE 4.

The drug-drug interaction index (R value) predicted from in vitro OATP1B1-mediated uptake of 1 μM rosuvastatin as inhibited by anti-TB drugs^a

Anti-TB drug	Drug-drug interaction index (R value)
	Ki (μM)	R value = 1 + [I]/Ki
		[I] = Cmax	[I] = [I]u inlet,max
PAS	32.0	27.5 ± 6.8	55.5 ± 12.3*
Rifabutin	12.3	0.05 ± 0.001	1.30 ± 0.31*
Ethambutol	29.8	1.20 ± 0.46	17.9 ± 3.40*
Linezolid	35.0	2.44 ± 0.62	2.19 ± 0.92*
Amoxicillin	13.0	2.56 ± 0.63	10.0 ± 2.4*
Rifapentine	11.0	1.60 ± 0.32	1.16 ± 0.54

^aThe R values were determined using the inhibition constant, K_i, with the maximum systemic concentration, C_max (bound + unbound), of the anti-TB drugs as [I] and the maximum unbound concentration inlet to the liver, [I]_{u inlet,max}, following the guidelines described in the text. The R value represents the mean ± SD from triplicate experiments. An asterisk indicates the result is significant according to FDA, MHLW, and EMA guidance for prototypical substrates in which the R values are greater than the corresponding cutoff values recommended by the regulatory authorities under both C_max (R ≥ 1.1, FDA) and [I]_{u inlet,max} (R ≥ 1.25, FDA and MHLW; R ≥ 1.04, EMA) conditions. The cutoff value is expressed as the suggested value according to the upper limit of the equivalence range by the FDA.