Table 1.
Observed and predicted pharmacokinetic parameters (mean ± SD) for baricitinib, probenecid, tofacitinib, midazolam, and simvastatin
| Verification purpose | Substrate | Population | Dose | Parameter | Observed | Predicted | Fold error of mean | References |
|---|---|---|---|---|---|---|---|---|
| Baricitinib | Baricitinib | Healthy population | 4 mg single | AUC0–∞ (h*ng/mL) | 236.0 ± 51.9 | 223.8 ± 85.4 | 0.95 | 14 |
| C max (ng/mL) | 36.2 ± 8.0 | 39.6 ± 12.9 | 1.09 | |||||
| CL/F (L/hour) | 16.9 ± 3.7 | 21.3 ± 10.0 | 1.26 | |||||
| CLR (L/hour) | 11.0 ± 2.4 | 12.3 ± 5.6 | 1.12 | |||||
| 4 mg single with probenecid | AUC0–∞ (hour*ng/mL) | 480.0 ± 67.2 | 410.8 ± 121.7 | 0.86 | 14 | |||
| C max (ng/mL) | 37.3 ± 7.5 | 46.3 ± 14.1 | 1.24 | |||||
| CL/F (L/hour) | 8.3 ± 1.2 | 10.8 ± 4.0 | 1.30 | |||||
| CLR (L/hour) | 3.4 ± 0.7 | 5.1 ± 1.5 | 1.49 | |||||
| Chinese healthy population | 4 mg single | AUC0–∞ (hour*ng/mL) | 274.0 ± 45.2 | 245.3 ± 80.4 | 0.90 | 18 | ||
| C max (ng/mL) | 51.3 ± 20.4 | 42.8 ± 13.8 | 0.83 | |||||
| CL/F (L/hour) | 15.0 ± 2.5 | 18.2 ± 6.5 | 1.22 | |||||
| Probenecid | Healthy population | 1000 mg b.i.d. | C max (µg/mL) | 145.0 | 165.9 | 1.14 | 14 | |
| AUCss (µg/mL) | 115.0 | 122.4 | 1.06 | |||||
| Tofacitinib | Tofacitinib | Healthy population | 10 mg single | AUC0–∞ (hour*ng/mL) | 268.0 ± 71.5 | 261.5 ± 89.3 | 0.98 | 19 |
| C max (ng/mL) | 94.2 ± 25.3 | 71.1 ± 24.8 | 0.75 | |||||
| Subjects with mild RI | 10 mg single | AUC0–∞ (hour*ng/mL) | 370.0 ± 109.0 | 327.5 ± 105.3 | 0.89 | 19 | ||
| C max (ng/mL) | 87.3 ± 23.2 | 74.5 ± 24.8 | 0.85 | |||||
| Subjects with moderate RI | 10 mg single | AUC0–∞ (hour*ng/mL) | 396.0 ± 154.0 | 359.2 ± 142.9 | 0.91 | 19 | ||
| C max (ng/mL) | 104.0 ± 47.5 | 75.4 ± 26.1 | 0.72 | |||||
| Subjects with severe RI | 10 mg single | AUC0–∞ (hour*ng/mL) | 615.0 ± 214.0 | 512.8 ± 173.0 | 0.83 | 18 | ||
| C max (ng/mL) | 111.0 ± 28.6 | 86.8 ± 31.8 | 0.78 | |||||
| Chinese healthy population | 10 mg single | AUC0–∞ (hour*ng/mL) | 277.1 ± 37.0 | 354.3 ± 118.6 | 1.28 | 20 | ||
| C max (ng/mL) | 105.3 ± 42.0 | 90.3 ± 28.3 | 0.86 | |||||
| Chinese geriatric population | Midazolam | Chinese elderly population (66‐75 years) | 15 mg single | AUC0–∞ (hour*ng/mL) | 229.0 ± 67.3 | 285.5 ± 243.5 | 1.25 | 16 |
| C max (ng/mL) | 98.0 ± 41.5 | 89.2 ± 83.6 | 0.91 | |||||
| CL/F (L/hour) | 74.6 ± 25.7 | 103.7 ± 101.1 | 1.39 | |||||
| Chinese elderly population (>76 years) | 15 mg single | AUC0–∞ (hour*ng/mL) | 254.0 ± 87.3 | 319.5 ± 269.0 | 1.26 | 16 | ||
| C max (ng/mL) | 96.8 ± 57.5 | 97.3 ± 75.8 | 1.01 | |||||
| CL/F (L/hour) | 66.0 ± 23.2 | 95.5 ± 88.1 | 1.45 | |||||
| Simvastatin | Chinese elderly population (60–91 years) | 20 mg QD | AUC0–∞ (hour*ng/mL) | 17.2 | 22.1 | 1.29 | 16 | |
| CL/F (L/hour) | 1020.0 | 1630.8 | 1.60 |
AUC0 – ∞, area under the curve from zero to infinity; AUCss, area under the curve at steady‐state; C max, peak plasma concentration; CL/F, apparent clearance; CLR, renal clearance; RI, renal impairment.