Table 2.
Overview of the clinical outcomes per study
| Reference | Clinical outcomes interaction | CYP2D6 profile | ||
|---|---|---|---|---|
| Pharmacokinetics | Pharmacodynamics | Other outcomes | ||
| O. Onalan et al. 33 | n/a | Complete AV‐Block | n/a | n/a |
| T. Walley et al. 19 | n/a | Bradycardia, lethargy | n/a | n/a |
| F. König et al. 18 | n/a | Bradycardia, lethargy | n/a | n/a |
| S. Stout et al. 27 |
↑mean AUC [S]‐metoprolol IR (270%, P < 0.001), ↑mean AUC [R]‐metoprolol IR (419%, P < 0.001), ↑mean AUC [S]‐metoprolol ER (246%, P < 0.001), ↑mean AUC [R]‐metoprolol ER (334%, P < 0.001),↓[S]/[R]‐ratio (29% and 30% for IR and ER resp., P < 0.001) |
↓mean systolic blood pressure (7.3%, P < 0.001) no changes in HR or P‐R interval observed between baseline and any of the study phases | n/a | n/a |
| R. Parker et al. 28 |
↑mean AUC [S]‐metoprolol IR (209%, P < 0.05) ↑mean AUC [R]‐metoprolol IR (288%, P < 0.05) ↑mean AUC [S]‐metoprolol 100 mg ER (220%, P < 0.05) ↑mean AUC [R]‐metoprolol 100 mg ER(220%, P < 0.05) ↑mean AUC [S]‐metoprolol 200 mg ER (210%, P < 0.05) ↑mean AUC [R]‐metoprolol 200 mg ER (297%, P < 0.05) ↓[S]/[R]‐ratio metoprolol IR (27%, P < 0.05) ↓[S]/[R]‐ratio metoprolol 100 mg ER (27%, P < 0.05) ↓[S]/[R]‐ratio metoprolol 200 mg ER (27%, P < 0.05) |
↓AUEC exercise HR IR formulation (12%, P < 0.05), ↓AUEC exercise HR 100 mg ER (8.6%, P < 0.05), ↓AUEC exercise HR 200 mg ER (9.5%, P < 0.05), ↓AUEC exercise systolic blood pressure IR formulation (7.5%, P < 0.05), ↓AUEC exercise systolic blood pressure 100 mg ER (9.2%, P < 0.05), ↓AUEC exercise systolic blood pressure 200 mg ER (11.1%, P < 0.05) |
n/a | CYP2D6*1/*1 (n = 3), CYP2D6*1/*2 (n = 4), Other [at least 1 active CYP2D6 allele] (n = 8) |
| A. Hemeryck et al. 29 | ↑mean AUC [S]‐metoprolol (408%, P < 0.001), ↑mean AUC [R]‐metoprolol (693%, P < 0.001) |
↑AUEC reduction in exercise HR (46%, P < 0.01)b
↑AUEC reduction in exercise systolic blood pressure (97%, P < 0.05)b |
n/a | Extensive metabolizers |
| K. Goryachkina et al. 30 | ↑mean AUC metoprolol (321%, P < 0.0001), ↓mean AUC α‐hydroxy‐metoprolol (77%, P < 0.0001), | ↓AUEC resting HR (13%, P = 0.0007) severe postural hypotension (n = 1)abradycardia [<45 BPM] (n = 1)a | n/a | CYP2D6*1/*1 (n = 9), CYP2D6*1/*3 (n = 3), CYP2D6*1/*4 (n = 5) |
| P.A. Kurdyak et al. 31 | n/a | Compared to fluvoxamine,citalopram, and venlafaxine, ‐metoprolol: Bradycardia (OR = 1.01, 95% CI 0.53–1.94) | n/a | |
| M.A. Bahar et al. 32 | n/a | n/a |
Compared to citalopram‐metoprolol: Early discontinuation of metoprolol (OR = 1.07, 95% CI:0.77–1.48); dose adjustment of metoprolol (OR = 1.00, 95% CI 0.65–1.54) Compared to mirtazepine‐metoprolol: Early discontinuation of metoprolol (OR = 1.43, 95% CI 1.01–2.02); dose adjustment of metoprolol (OR = 1.00, 95% CI 0.65–1.54) |
n/a |
AUC, Area under the Concentration Curve; AUEC, Area under the Effect Curve; BPM, Beats per minute; ER, Extended Release; HR, Heart Rate; IR, Immediate Release; MR, Metabolic Ratio; OR, Odds Ratio.
a
Patient carrying one non‐functional CYP2D6 allele.
b
% change from the baseline (before metoprolol intake) in 4‐min exercise tests.