Pharmacokinetic variables of desloratadine, 3-hydroxydesloratadine, and 3-hydroxydesloratadine-O-glucuronide in 11 healthy subjects who ingested placebo, clopidogrel (300 mg on day 3, and 75 mg on days 4 and 5), or gemfibrozil (600 mg BID for 5 days). On day 3 of each study phase, a single 5 mg dose of desloratadine was administered 1 hour after pretreatment.
Data are given as geometric mean with geometric coefficient of variation (in brackets), except for tmax, which is given as median with range. The geometric mean ratios between the clopidogrel and placebo phases and gemfibrozil and clopidogrel phases are given with 90% CI (in brackets).
| Variable | Placebo Phase | Clopidogrel Phase | Clopidogrel to Placebo Phase Ratio (90% CI) | Gemfibrozil Phase | Gemfibrozil to Placebo Phase Ratio (90% CI) | Gemfibrozil to Clopidogrel Phase Ratio (90% CI) |
|---|---|---|---|---|---|---|
| Desloratadine | ||||||
| Cmax (ng/ml) | 2.83 (43) | 4.65 (28) | 1.65 (1.33–2.04)*** | 4.93 (34) | 1.74 (1.37–2.21)*** | 1.06 (0.90–1.24); P > 0.9 |
| tmax (h) | 4 (1.0–7.0) | 4.0 (4.0–7.0) | P = 0.4 | 4.0 (3.0–7.0) | P > 0.9 | P > 0.9 |
| t1/2 (h) | 17 (19) | 26 (18) | 1.5 (1.3–1.8)*** | 39 (19) | 2.2 (2.0–2.5)*** | 1.5 (1.2–1.8)††† |
| AUC0–71h (ng × h/ml) | 44.3 (55) | 111 (32) | 2.51 (2.05–3.07)*** | 156 (27) | 3.51 (2.67–4.63)*** | 1.40 (1.24–1.59)††† |
| AUC0–∞ (ng × h/ml) | 46.8 (56) | 131 (36) | 2.80 (2.32–3.38)*** | 216 (28) | 4.62 (3.46–6.16)*** | 1.65 (1.42–1.91)††† |
| 3-Hydroxydesloratadine | ||||||
| Cmax (ng/ml) | 1.29 (24) | 0.388 (34) | 0.30 (0.25–0.37)*** | 0.05 (42) | 0.04 (0.03–0.05)*** | 0.13 (0.10–0.17)††† |
| tmax (h) | 4.0 (4.0–7.0) | 4.0 (4.0–11.0) | P = 0.2 | 11.0 (7.0–11.0) | P = 0.009 | P = 0.021 |
| t1/2 (h) | 25 (13) | 51 (40) | 2.0 (1.7–2.4)*** | N/A | — | — |
| AUC0–71h (ng × h/ml) | 29.5 (27) | 15.4 (30) | 0.52 (0.44–0.62)*** | 1.81 (54) | 0.06 (0.04–0.09)*** | 0.12 (0.09–0.16)††† |
| AUC0–∞ (ng × h/ml) | 34.3 (28) | 25.5 (30) | 0.74 (0.69–0.80)*** | N/A | — | — |
| 3-Hydroxydesloratadine:desloratadine AUC0–71h ratio | 0.666 (53) | 0.139 (47) | 0.21 (0.18–0.24)*** | 0.012 (70) | 0.017 (0.013–0.024)*** | 0.08 (0.07–0.11)††† |
| 3-Hydroxydesloratadine-O-glucuronide | ||||||
| Cmax (ng/ml) | 35.0 (40) | 13.0 (34) | 0.37 (0.31–0.45)*** | 1.32 (54) | 0.04 (0.02–0.06)*** | 0.10 (0.07–0.15)††† |
| tmax (h) | 9.0 (7.0–11.0) | 9.0 (7.0–11) | P = 0.9 | 11.0 (11.0–23.0) | P = 0.03 | P = 0.048 |
| t1/2 (h) | 19 (18) | 35 (36) | 1.9 (1.6–2.2)*** | N/A | — | — |
| AUC0–71h (ng × h/ml) | 863 (32) | 475 (25) | 0.55 (0.46–0.65)*** | 54.5 (47) | 0.06 (0.04–0.10)*** | 0.11 (0.09–0.15††† |
| AUC0–∞ (ng × h/ml) | 940 (32) | 666 (18) | 0.71 (0.62–0.81)*** | N/A | — | — |
N/A, not applicable.
↵***P < 0.001 vs. placebo phase, †††P < 0.001 vs. clopidogrel phase.