Table 3.
Kinetic disposition of the α-hydroxymetoprolol (OHM) and O-demethylmetoproloic acid (AODM) isomers in the control (n = 13) and diabetes (n = 10) groups (median and 95% CI)
| Isomer | Cmax (ng ml−1) | tmax (h) | AUC(0,∞) (ng ml−1 h) | t1/2 (h) | Kel (h−1) | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Control group | Diabetes group | Control group | Diabetes group | Control group | Diabetes group | Control group | Diabetes group | Control group | Diabetes group | |
| 1′S,2R-OHM | 9.64#♦ (7.34, 11.35) | 6.48#♦ (4.42, 11.51) | 2.00 (1.24, 2.37) | 3.00* (2.30, 5.04) | 57.27#♦ (48.37, 66.38) | 54.29#♦ (42.16, 71.49) | 5.87 (4.95, 7.50) | 5.36 (4.09, 8.56) | 0.11 (0.10, 0.15) | 0.13 (0.10, 0.15) |
| 1′S,2S-OHM | 11.31♣⊗ (8.41, 13.52) | 7.25♣⊗ (4.93, 12.39) | 2.00 (1.25, 2.52) | 2.75* (1.92, 4.38) | 79.76♣⊗ (60.48, 88.39) | 59.84♣⊗ (46.26, 81.79) | 6.31 (5.50, 7.50) | 6.20 (4.82, 8.47) | 0.11 (0.10, 0.13) | 0.11 (0.10, 0.15) |
| 1′R,2R-OHM | 26.14 (19.50, 30.24) | 18.56 (14.93, 31.05) | 2.00 (1.21, 2.49) | 3.00* (2.36, 5.04) | 168.52 (136.69, 183.94) | 171.37 (140.63, 202.29) | 6.48 (5.32, 6.77) | 5.53 (4.72, 7.57) | 0.11 (0, 0.13) | 0.12 (0.10, 0.15) |
| 1′R,2S-OHM | 33.68 (25.08, 40.39) | 28.45 (19.62, 42.51) | 2.00 (1.27, 2.50) | 3.00* (2.25, 5.05) | 223.99 (179.47, 254.32) | 248.09 (175.26, 316.34) | 5.95 (5.16, 6.55) | 5.74 (4.11, 8.13) | 0.12 (0.11, 0.13) | 0.12 (0.11, 0.17) |
| R-(+)-AODM | 523.63 (430.52, 610.87) | 456.86 (384.48, 640.91) | 2.00 (1.95, 3.12) | 3.50* (2.83, 5.17) | 2769.70 (2429.10, 3795.20) | 3678.80* (3375.00, 4604.80) | 4.59 (3.35, 6.52) | 5.85* (5.10, 7.89) | 3.62 (2.95, 4.62) | 5.42* (4.93, 5.98) |
| S-(–)-AODM | 505.34▪ (402.84, 564.65) | 459.96 (367.73, 635.23) | 2.00 (1.90, 3.10) | 3.00* (2.64, 4.96) | 2660.40▪ (2213.30, 3482.40) | 3414.90*▪ (3018.40, 4180.10) | 0.15 (0.12, 0.21) | 0.12 (0.09, 0.14) | 0.18 (0.15–0.23) | 0.13* (0.11–0.14) |
Kruskal-Wallis test for paired data, P < 0.05: #1′S.2R vs. 1′R.2R; ♣1′S.2S vs. 1′R.2R; ♦1′S.2R vs. 1′R.2S; ⊗1′S.2S vs. 1′R.2S. ▪Wilcoxon test for paired data, P < 0.05 (R-(+)-AODM vs. S-(–)-AODM) *Mann–Whitney test, P < 0.05 (Control group vs. diabetes group). AUC(0,∞), area under the curve for plasma concentration vs. time; Cmax, maximum plasma concentration; Kel, elimination rate constant; t1/2, elimination half-life; tmax, time needed to reach Cmax.