Pharmacokinetic variables of clopidogrel, the clopidogrel active cis-5-thiol metabolite, clopidogrel carboxylic acid, and clopidogrel acyl-β-d-glucuronide in 12 healthy volunteers after 300-mg (day 1) and 75-mg dose (day 3) of clopidogrel, which was ingested 1 hour before simvastatin.
Data are given as the median with the range.
| Variable | Clopidogrel 300 mg (Day 1) | Clopidogrel 75 mg (Day 3) |
|---|---|---|
| Clopidogrel | ||
| Cmax (ng/ml) | 2.87 (1.21–7.28) | 0.33 (0.22–2.74) |
| tmax (hours) | 1.5 (0.92–2.0) | 0.92 (0.92–1.5) |
| t1/2 (hours) | 0.90 (0.63–1.6) | 1.6 (0.82–2.3) |
| AUC0–4 hours (ng∙h/ml) | 5.42 (2.04–10.4) | 0.68 (0.40–4.56) |
| AUC0–∞ (ng∙h/ml) | 5.98 (2.15–11.0) | 0.91 (0.50–4.77) |
| Clopidogrel active metabolite | ||
| Cmax (ng/ml) | 23.2 (12.3–45.2) | 7.12 (3.29–14.6) |
| tmax (hours) | 0.92 (0.92–1.5) | 0.92 (0.92–0.92) |
| t1/2 (hours) | 0.52 (0.41–0.57) | 0.59 (0.43–0.94) |
| AUC0–4 hours (ng∙h/ml) | 30.9 (16.3–59.4) | 7.61 (3.64–13.9) |
| AUC0–∞ (ng∙h/ml) | 31.2 (16.9–60.3) | 7.69 (3.68–14.1) |
| Clopidogrel carboxylic acid | ||
| Cmax (ng/ml) | 9820 (6760–23,600) | 2270 (1070–5730) |
| tmax (hours) | 0.92 (0.92–1.5) | 0.92 (0.92–0.92) |
| t1/2 (hours) | 1.7 (1.2–2.5) | 2.4 (1.4–3.3) |
| AUC0–4 hours (ng∙h/ml) | 19,700 (13,700–44,800) | 4020 (2380–9640) |
| AUC0–∞ (ng∙h/ml) | 27,800 (17,000–67,600) | 6260 (3920–12,300) |
| Clopidogrel acyl-β-d-glucuronide | ||
| Cmax (ng/ml) | 2310 (1000–4440) | 832 (359–1810) |
| tmax (hours) | 1.5 (0.92–2.0) | 0.92 (0.92–1.5) |
| t1/2 (hours) | 2.1 (1.5–5.0) | 1.6 (1.0–2.1) |
| AUC0–4 hours (ng∙h/ml) | 5460 (2380–12,600) | 1530 (747–3600) |
| AUC0–∞ (ng∙h/ml) | 7990 (3300–33,400) | 1930 (923–4630) |