TABLE 4.

Between‐group differences in protein expression and in vivo activities of CYP2C19, CYP3A, CYP1A2, and CYP2C9

Parameter	T2DM‐obesity vs. Obesity
CYP2C19 a
5‐OH‐omeprazole/omeprazole	−0.39 [−0.82, −0.09]
Jejunal CYP2C19 (fmol/μg protein) b , c	−0.09 [−0.18, −0.003]
Hepatic CYP2C19 (fmol/μg protein) d	−0.83 [−3.4, 0.97]
CYP3A e
MDZ absolute bioavailability (%)	4.4 [−1.2, 11]
MDZ systemic clearance (L/h)	1.9 [−3.7, 7.0]
4βOHC (ng/ml)	0.70 [−1.2, 2.7]
Jejunal CYP3A4 (fmol/μg protein) b	−1.6 [−5.6, 2.0]
Hepatic CYP3A4 (fmol/μg protein) d	−3.3 [−7.3, 0.81]
CYP1A2 f
Paraxanthine/caffeine	0.02 [−0.03, 0.08]
Hepatic CYP1A2 (fmol/μg protein) d	−0.11 [−3.9, 3.8]
CYP2C9 g
LCA/losartan	−0.16 [−0.42, 0.09]
Jejunal CYP2C9 (fmol/μg protein) b	1.5 [1.2, 2.0]
Hepatic CYP2C9 (fmol/μg protein) d	0.04 [−1.7, 1.7]

Note: Data are presented as median [95% confidence interval].

Wilcoxon rank‐sum test was used to compare differences between the groups. A p value <0.05 was considered statistically significant (shown in bold).

Abbreviations: 4βOHC, 4β‐hydroxycholesterol CYP; cytochrome P450; LCA, losartan carboxylic acid; MDZ, midazolam; NA, not available; T2DM, type 2 diabetes mellitus.

^a CYP2C19 activity was described by the 3‐h plasma 5‐OH‐omeprazole/omeprazole ratio.

^b Jejunal biopsies were only available in 37 patients subjected to Roux‐en‐Y‐gastric bypass (RYGB).

^c Jejunal CYP2C19 concentration was missing in 3 patients due to technical error (n = 34).

^d Hepatic biopsies were only available in 56 patients subjected to RYGB or cholecystectomy.

^e CYP3A activity was described by absolute bioavailability and systemic clearance of midazolam and plasma concentrations of the endogenous CYP3A4 biomarker 4βOHC.

^f CYP1A2 activity was described by the 4‐h plasma paraxanthine/caffeine ratio.

^g CYP2C9 activity was described by the 8‐h urine losartan/LCA ratio.