Table 3.
Comparison of pharmacokinetics of afatinib and characteristics between patients with grades 2 and 0–1 diarrhea.
| Parameters/Characteristics | Grade 2 Diarrhea | Grade 0–1 Diarrhea | p-Value |
|---|---|---|---|
| Median (Quartile 1–Quartile 3) | Median (Quartile 1–Quartile 3) | ||
| Cmax (ng/mL) | 78.0 (47.9–84.1) | 38.9 (32.8–55.0) | 0.017 |
| C0 (ng/mL) | 38.9 (33.1–42.0) | 21.0 (15.0–29.8) | 0.032 |
| Cmin (ng/mL) | 28.1 (24.8–34.4) | 16.5(14.5–25.0) | 0.046 |
| Cmax/Cmin ratio | 2.20 (1.90–2.70) | 2.20 (1.75–2.45) | 0.657 |
| AUC0–24 (ng·h/mL) | 1225 (891–1344) | 666 (580–863) | 0.013 |
| AUC6–24 (ng·h/mL) | 787 (672–950) | 500 (424–592) | 0.007 |
| AUC6–24/AUC0–24 × 100 (%) | 71.7 (67.8–73.3) | 73.6 (69.7–75.8) | 0.389 |
| Daily dose, 30 mg:40 mg | 1:8 | 6:13 | 0.249 |
| Female:male | 6:3 | 7:12 | 0.142 |
| Age, years | 65.0 (62.0–71.0) | 67.0 (63.5–73.5) | 0.693 |
| Body weight, kg | 50.5 (46.7–56.0) | 56.2 (53.2–64.3) | 0.085 |
| Body surface area, m2 | 1.54 (1.41–1.57) | 1.60 (1.54–1.73) | 0.109 |
| BMI, kg/m2 | 22.9 (22.8–23.3) | 23.0 (21.3–23.4) | 0.694 |
| Laboratory test values | |||
| White blood cell, ×103/mm3 | 5.3 (4.0–6.9) | 5.4 (4.1–6.0) | 0.825 |
| Red blood cell, ×104/mm3 | 405 (384–430) | 413 (372–455) | 0.640 |
| Hemoglobin, g/dL | 12.1 (11.5–12.4) | 12.5 (11.5–13.6) | 0.403 |
| Platelets, ×104/mm3 | 21.4 (16.6–23.1) | 23.7 (20.6–27.2) | 0.210 |
| Aspartate aminotransferase, IU/L | 21 (18–22) | 19 (18–28) | 0.730 |
| Alanine aminotransferase, IU/L | 15 (11–28) | 18 (14–25) | 0.362 |
| Alkaline phosphatase, IU/L | 241 (211–419) | 261 (226–290) | 0.825 |
| Lactate dehydrogenase, IU/L | 174 (156–191) | 176 (160–217) | 0.980 |
| Serum albumin, g/dL | 3.4 (3.3–3.6) | 3.7 (3.4–3.9) | 0.311 |
| Total bilirubin, mg/dL | 0.5 (0.4–0.7) | 0.5 (0.4–0.6) | 0.439 |
| Serum creatinine, mg/dL | 0.67 (0.56–0.70) | 0.74 (0.66–0.85) | 0.110 |
| eGFR, mL/min/1.73 m2 | 78.5 (62.3–97.3) | 74.1 (65.9–82.6) | 0.539 |
Data are presented as number or median (quartile 1–quartile 3). Cmax, maximum plasma concentration; C0, pre-dose concentration; Cmin, minimum plasma concentration; AUC0–24 and 6–24, area under the plasma concentration–time curve from 0 to 24 h and 6 to 24 h, respectively; eGFR, estimated glomerular filtration rate.