Table 3.
Pharmacokinetic parameters of analytes between control and NASH mice by intragastric administration.
| Analytes | Groups | AUC(0-12h), ng·h/mL | AUC(0-infinity), ng·h/mL | Cmax, ng/mL | Tmax, h | t1/2, h | CLz/F, L/h/kg |
|---|---|---|---|---|---|---|---|
| Omeprazole | Control | 525.43 ± 67.62 | 549.67 ± 59.45 | 758.00 ± 242.89 | 0.11 ± 0.04 | 4.33 ± 2.78 | 18,362.04 ± 1,836.04 |
| NASH | 1765.71 ± 684.29*** | 1821.70 ± 731.27*** | 965.67 ± 340.37 | 0.22 ± 0.16 | 2.67 ± 1.07 | 7116.28 ± 5250.54*** | |
| 5-OH-omeprazole | Control | 73.49 ± 28.59 | 74.04 ± 28.25 | 229.98 ± 93.95 | 0.10 ± 0.03 | 0.51 ± 0.31 | 89248.71 ± 124294.64 |
| NASH | 36.46 ± 11.66* | 57.26 ± 28.94 | 53.00 ± 16.46*** | 0.15 ± 0.10 | 1.50 ± 0.73* | 215121.12 ± 104444.70 | |
| Phenacetin | Control | 134.92 ± 42.61 | 143.64 ± 41.11 | 199.33 ± 106.23 | 0.10 ± 0.03 | 4.59 ± 1.87 | 75382.89 ± 24126.47 |
| NASH | 231.43 ± 126.05* | 314.64 ± 197.88* | 423.95 ± 319.05* | 0.10 ± 0.03 | 7.78 ± 3.88 | 42948.82 ± 23087.23** | |
| Acetaminophen | Control | 609.00 ± 215.27 | 1291.43 ± 679.24 | 712.14 ± 243.35 | 0.11 ± 0.04 | 6.23 ± 3.88 | 14547.78 ± 3328.31 |
| NASH | 1277.79 ± 677.38* | 1291.43 ± 679.24 | 1042.67 ± 623.48 | 0.28 ± 0.25 | 1.72 ± 1.04* | 9374.47 ± 3743.18* | |
| Midazolam | Control | 302.17 ± 58.88 | 303.44 ± 58.44 | 358.29 ± 135.28 | 0.13 ± 0.07 | 2.13 ± 0.66 | 34263.46 ± 8162.03 |
| NASH | 1518.64 ± 790.20*** | 1521.71 ± 791.59*** | 988.17 ± 655.44** | 0.24 ± 0.145 | 1.54 ± 0.31 | 11891.56 ± 14110.88** | |
| OH-midazolam | Control | 2561.26 ± 558.16 | 2574.50 ± 556.76 | 1123.71 ± 225.50 | 0.37 ± 0.28 | 1.48 ± 0.35 | 4032.33 ± 805.79 |
| NASH | 10885.25 ± 4549.00*** | 11510.02 ± 5062.40*** | 2347.17 ± 962.87** | 0.96 ± 0.40** | 2.61 ± 0.71** | 1289.74 ± 1256.38*** | |
| Tolbutamide | Control | 3069.03 ± 3378.87 | 3123.13 ± 3422.15 | 669.43 ± 508.15 | 0.98 ± 1.45 | 1.78 ± 0.47 | 742.03 ± 557.94 |
| NASH | 21686.36 ± 15503.09** | 56355.58 ± 49559.98* | 2471.67 ± 2023.48* | 5.67 ± 1.51*** | 28.07 ± 24.80** | 33.46 ± 24.09** | |
| OH-Tolbutamide | Control | 324.32 ± 258.43 | 329.04 ± 260.28 | 56.17 ± 28.47 | 2.14 ± 0.90 | 1.66 ± 0.74 | 3024.55 ± 4818.47 |
| NASH | 1339.71 ± 1043.23* | 1630.81 ± 1040.30* | 159.04 ± 91.64* | 11.33 ± 1.63*** | 10.94 ± 8.48* | 251.87 ± 300.30 | |
| Chlorzoxazone | Control | 250.06 ± 88.36 | 271.46 ± 99.36 | 276.37 ± 105.55 | 0.14 ± 0.04 | 4.30 ± 2.23 | 3.99 ± 0.98 |
| NASH | 602.00 ± 267.84** | 629.87 ± 251.86** | 571.87 ± 299.33* | 0.19 ± 0.09 | 3.44 ± 2.74 | 1.88 ± 0.88*** | |
| 6-OH-chlorzoxazone | Control | 224.10 ± 35.78 | 510.70 ± 602.95 | 64.96 ± 27.38 | 0.26 ± 0.12 | 29.58 ± 48.45 | 2.92 ± 1.86 |
| NASH | 266.55 ± 114.43 | 484.46 ± 348.08 | 49.313 ± 24.289 | 3.10 ± 3.58 | 10.30 ± 7.93 | 3.48 ± 2.66 | |
| Metoprolol | Control | 317.71 ± 128.62 | 328.84 ± 127.43 | 216.40 ± 93.22 | 0.12 ± 0.09 | 2.52 ± 0.69 | 3.41 ± 1.20 |
| NASH | 413.45 ± 218.46 | 453.42 ± 298.21 | 189.13 ± 88.97 | 0.27 ± 0.32 | 2.60 ± 1.44 | 2.92 ± 1.59 | |
| α-OH-metoprolol | Control | 59.11 ± 21.21 | 61.32 ± 21.90 | 47.40 ± 17.72 | 2.77 ± 1.51 | 0.14 ± 0.09 | 2.77 ± 1.51 |
| NASH | 68.28 ± 40.72 | 70.39 ± 43.97 | 37.77 ± 11.34 | 1.70 ± 1.01 | 0.23 ± 0.23 | 1.70 ± 1.01 |
Note: AUC(0–12 h): area under the plasma concentration–time curve from 0 to 12 h; AUC(0-infinity): area under the plasma concentration–time curve from 0 to infinity h; Cmax: maximal concentration; t1/2: eliminate half-life; Tmax: time to peak concentration; CLz/F: blood clearance. Data are mean ± SD, n = 8; *p < 0.05, **p < 0.01, ***p < 0.001 versus control group.