TABLE 5.

Estimated impact on oral bioavailability (F) of OCT1 substrates caused by inhibition of intestinal and/or hepatic OCT1 and observed clinical data.

Scenario	Atenolol	Metoclopramide	Metformin	Trospium
No inhibition of intestinal and hepatic OCT1	0.425	0.714	0.48	0.095
Predicted inhibition of intestinal OCT1 (assuming apical localization)	0.213 (↓50%)	0.357 (↓50%)	0.24 (↓50%)	0.048 (↓50%)
Predicted inhibition of hepatic OCT1 only (i.v. administration or basolateral intestinal OCT1)	0.463 (↑9%)	0.777 (↑9%)	0.54 (↑13%)	0.098 (↑3%)
Predicted inhibition of intestinal (apical) and hepatic OCT1 (oral administration)	0.231 (↓46%)	0.389 (↓46%)	0.27 (↓44%)	0.049 (↓49%)
Observed interaction data	unchanged AUC Houtzagers et al. (1982)	AUC↑, 13% Leucuţa et al. (2004)	unchanged AUC Oefelein et al. (2013)	unchanged AUC Abebe et al. (2020)

Used data for estimations: Atenolol (fa, 0.5; fh, 0.85), Metoclopramide (fa, 0.84; fh, 0.85); Metformin (fa, 0.6; fh, 0.8) and Trospium (fa, 0.1; fh, 0.95). In the case of inhibition, 50% reduction of intestinal absorption or hepatic extraction was assumed. As data on fh were not available, they have been indirectly estimated from excretion pathways (fh ∼ renal excretion after i.v. administration).