TABLE 1

IVIVE of fexofenadine and erythromycin CL_hepatic utilizing in vitro CL_{int, uptake} measurements demonstrating the impact of elacridar

	CL_{int, uptake}^{^a} (µl/min/10⁶ cells)	Predicted CL_blood^{^b} (ml/min/kg)	Predicted CL_hepatic^{^c} (ml/min/kg)	In vivo CL_blood^{^d} (ml/min/kg)	In vivo CL_hepatic^{^c} (ml/min/kg)	Fold Error CL_hepatic (Observed/ Predicted)
Rat, fexofenadine
Control	1.92 ± 0.8	1.7 ± 0.7	1.1 ± 0.5	10.9 ± 3.4	7.2 ± 2.7	6.5
Elacridar, 1 µM	4.6 ± 1.6**	3.8 ± 1.3*	2.5 ± 0.9*			2.9
Elacridar, 2 µM	7.6 ± 1.1**	6.0 ± 0.8**	4.1 ± 0.6**			1.8
Human, erythomycin
Control	4.4 ± 0.3	1.9 ± 0.3	1.9 ± 0.3	8.8 ± 2.2	8.5 ± 2.2	4.5
Elacridar, 0.5 µM	5.7 ± 0.8**	2.4 ± 0.4**	2.4 ± 0.4**			3.6

Mean ± SD, n = 3; ***P < 0.001, **P < 0.01, *P < 0.05, significantly different from control experiments without elacridar.
↵a CL_{int, uptake} was measured using suspended hepatocytes.
↵b CL_blood was predicted from CL_{int, uptake} using the well-stirred model, as described (Sohlenius-Sternbeck et al., 2012).
↵c CL_hepatic was calculated from CL_blood using data from Swift et al. (2009).
↵d In vivo CL_blood was measured in house in Sprague-Dawley rats (Lundquist P et al., 2014). Human pharmacokinetic parameters are from Sun et al. (2010).