Table 5

Prediction of the in vivo interaction between metoprolol and paroxetine, based on in vitro substrate depletion experiments with (R)- and (S)-metoprolol in the absence and in the presence of 0.08 μM unbound paroxetine in the incubation mixture

Substrate	Unbound Paroxetine	CL_int	Predicted AUC Ratio^5-a	Observed AUC Ratio^5-b
	μM	μl/min/mg
(R)-Metoprolol	0	3.94
	0.08	1.57
			2.5	10.5 (4.6–21.4)
(S)-Metoprolol	0	2.54
	0.08	1.48
			1.7	6.7 (3.2–14.4)

↵5-a Calculated according to eq.8.
↵5-b In vivo observed AUC ratio (range) in the presence and in the absence of paroxetine (Hemeryck et al., 2000).