TABLE 2.
Pharmacokinetic parameters of midazolam and dabigatran.
| Drugs | Healthy young adults | Healthy elderly | Elderly patients with chronic kidney disease | ||||
|---|---|---|---|---|---|---|---|
| Microdose | Microdose + Rifampicin | Microdose | Microdose | ||||
| GM (95%CI) | GM (95%CI) | GMR (95%CI) | GM (95%CI) | GMR (95%CI) | GM (95%CI) | GMR (95%CI) | |
| Midazolam | |||||||
| AUC0-last (pg/mL.hr) | 192 (155–237) | 248 (198–309) | 1.29 (0.96–1.74) | 440 (342–567) | 2.30 (1.70–3.09)* | 556 (454–681) | 2.90 (2.16–3.88)* |
| AUC0-inf (pg/mL.hr) | 200 (162–247) | 256 (206–318) | 1.28 (0.96–1.72) | 464 (365–590) | 2.32 (1.74–3.10)* | 579 (475–705) | 2.90 (2.18–3.85)* |
| Cmax (pg/mL) | 80 (67–96) | 78 (96–118) | 1.20 (0.92–1.56) | 151 (119–191) | 1.88 (1.44–2.44)* | 156 (132–185) | 1.95 (1.51–2.52)* |
| Tmax (hr)a | 0.7 (0.7–0.7) | 0.7 (0.7–0.8) | − | 0.7 (0.7–1.0) | − | 0.7 (0.7–1.0) | − |
| T1/2 (hr)a | 2.7 (2.1–3.4) | 2.5 (1.8–3.0) | − | 5.9 (4.0–7.7)* | − | 7.3 (5.3–8.1)* | − |
| CL/F (mL/min/kg0.75) | 127 (105–152) | 98 (81–118) | 0.77 (0.60–1.00) | 53 (42–67) | 0.42 (0.32–0.55)* | 39 (32–47) | 0.31 (0.23–0.40)*,¶ |
| Dabigatran | |||||||
| AUC0-last (pg/mL.hr) | 2,661 (2,147–3,298) | 6,228 (5,165–7,511) | 2.34 (1.78–3.08)* | 4,118 (3,136–5,408) | 1.55 (1.13–2.12)* | 10,930 (8,714–13,708) | 4.11 (3.01–5.61)*,¶ |
| AUC0-inf (pg/mL.hr) | 3,111 (2,577–3,757) | 6,902 (5,849–8,146) | 2.22 (1.74–2.83)* | 4,557 (3,554–5,844) | 1.46 (1.09–1.97)* | 13,242 (10,480–16,732) | 4.26 (3.18–5.70)*,¶ |
| Cmax (pg/mL) | 375 (302–467) | 699 (593–824) | 1.86 (1.43–2.43)* | 477 (378–601) | 1.27 (0.94–1.73) | 640 (506–808) | 1.70 (1.26–2.30)* |
| Tmax (hr)a | 1.5 (1.0–1.5) | 2.0 (2.0–2.5)* | − | 1.5 (1.0–1.5) | − | 1.5 (1.0–2.0) | − |
| T1/2 (hr)a | 6.6 (4.6–7.8) | 7.4 (5.8–10.6) | − | 6.9 (5.9–8.2) | − | 16.8 (14.5–21.7)*,¶ | − |
| CL/F (mL/min/kg0.75) | 228 (190–274) | 97 (85–112) | 0.43 (0.34–0.53)* | 141 (109–184) | 0.62 (0.47–0.83)* | 49 (40–61) | 0.22 (0.16–0.29)*,¶ |
| CLR, mL/min | 78 (70–88) | 59 (53–66) | 0.76 (0.65–0.88)* | 48 (39–59) | 0.61 (0.48–0.78)* | 15 (12–18) | 0.19 (0.15–0.24)*,¶ |
a
Data are presented in the median (interquartile range).
*p-value <0.05, healthy young adult as a reference group.
¶p-value <0.05, healthy elderly as a reference group.
AUC0-inf: area under the concentration-time curve of time zero to infinity; AUC0-last: area under the concentration-time curve of time zero to the last time point; CI: confidence interval; CL/F: oral clearance; CLR: renal clearance; Cmax: maximum plasma concentration; GM: geometric mean; GMR: geometric mean ratio; Tmax: time to maximum plasma concentration; T1/2: half-life.