Pharmacokinetic variables of simvastatin (lactone) and simvastatin acid in 12 healthy volunteers who ingested a single dose of placebo or 300 mg of clopidogrel on day 1, 75 mg of clopidogrel on days 2–3, and a single 40-mg dose of simvastatin 1 hour after placebo and 1 hour after clopidogrel on days 1 and 3 of clopidogrel administration
Data are given as the geometric mean, with the geometric coefficient of variation, tmax, as the median with the range. The geometric mean ratios between the two phases are given with 90% CI.
| Variable | Placebo (Control) | Clopidogrel 300 mg (Day 1) | Clopidogrel 75 mg (Day 3) |
|---|---|---|---|
| Simvastatin | |||
| Cmax (ng/ml) | 7.71 (63) | 10.1 (115) | 8.02 (118) |
| Ratio to control (90% CI) | 1.32 (0.95–1.83) | 1.04 (0.76–1.42) | |
| tmax (hours) | 1.5 (0.50–4.0) | 1.0 (0.50–5.0) | 1.5 (1.0–5.0) |
| t1/2 (hours) | 3.9 (65) | 4.1 (36) | 3.1 (30) |
| Ratio to control (90% CI) | 1.03 (0.81–1.30) | 0.79 (0.58–1.07) | |
| AUC0–2 hours (ng∙h/ml) | 7.84 (93) | 12.2 (107)* | 5.88 (133) |
| Ratio to control (90% CI) | 1.56 (1.16–2.09) | 0.75 (0.50–1.12) | |
| AUC0–12 hours (ng∙h/ml) | 28.4 (53) | 37.6 (86) | 27.4 (89) |
| Ratio to control (90% CI) | 1.32 (1.02–1.72) | 0.96 (0.79–1.18) | |
| AUC0–∞ (ng∙h/ml) | 34.9 (61) | 44.6 (90) | 29.9 (96) |
| Ratio to control (90% CI) | 1.28 (1.00–1.64) | 0.86 (0.67–1.10) | |
| Simvastatin acid | |||
| Cmax (ng/ml) | 2.43 (41) | 2.60 (77) | 2.58 (51) |
| Ratio to control (90% CI) | 1.07 (0.78–1.46) | 1.06 (0.89–1.26) | |
| tmax (hours) | 4.0 (2.0–5.0) | 4.0 (1.5–9.0) | 4.5 (3.0–7.0) |
| t1/2 (hours) | 4.9 (40) | 4.5 (53) | 4.4 (47) |
| Ratio to control (90% CI) | 0.91 (0.68–1.22) | 0.89 (0.65–1.24) | |
| AUC0–2 hours (ng∙h/ml) | 1.16 (84) | 1.72 (98)* | 0.76 (94) |
| Ratio to control (90% CI) | 1.48 (1.09–2.01) | 0.66 (0.42–1.03) | |
| AUC0–12 hours (ng∙h/ml) | 16.6 (43) | 18.6 (70) | 17.7 (60) |
| Ratio to control (90% CI) | 1.12 (0.83–1.50) | 1.06 (0.87–1.30) | |
| AUC0–∞ (ng∙h/ml) | 22.8 (44) | 25.0 (62) | 23.0 (77) |
| Ratio to control (90% CI) | 1.10 (0.80–1.50) | 1.01 (0.75–1.35) |
↵* P < 0.05 versus placebo.