Pharmacokinetic variables of pioglitazone and its metabolites M-IV and M-III in 10 healthy volunteers who ingested placebo on days 1, 2, and 3, or 300 mg clopidogrel on day 1, and 75 mg clopidogrel on days 2 and 3, and a single 15-mg dose of pioglitazone 1 hour after the administration of placebo or clopidogrel on day 1
Data are given as geometric mean with geometric coefficient of variation, tmax as median with range. The geometric mean ratios between the two phases are given with 90% CI.
| Variable | Placebo Phase (Control) | Clopidogrel Phase | Ratio to Control (90% CI) | |
|---|---|---|---|---|
| Pioglitazone | Cmax (ng/ml) | 642 (38) | 656 (46) | 1.02 (0.77–1.35) |
| C24 (ng/ml) | 39.6 (82) | 179 (42)*** | 4.52 (3.17–6.45) | |
| tmax (h) | 2.0 (2.0–4.0) | 3.0 (2.0–4.0)* | ||
| t1/2 (h) | 6.7 (14) | 11 (37)** | 1.66 (1.35–2.04) | |
| AUC0–72h (ng⋅h/ml) | 5580 (39) | 11700 (36)*** | 2.09 (1.69–2.59) | |
| AUC0–∞ (ng⋅h/ml) | 5580 (39) | 12000 (36)*** | 2.14 (1.76–2.61) | |
| M-IV | Cmax (ng/ml) | 263 (25) | 162 (30)* | 0.61 (0.48-0.79) |
| tmax (h) | 12 (9.0–24) | 24 (24–48)* | ||
| t1/2 (h) | 21 (15) | 38 (55)* | 1.74 (1.30–2.32) | |
| AUC0–72h (ng⋅h/ml) | 10200 (19) | 8050 (26) | 0.79 (0.65-0.97) | |
| AUC0–∞ (ng⋅h/ml) | 11600 (19) | 12200 (32) | 1.05 (0.90–1.22) | |
| M-IV-to-pioglitazone AUC0–∞ ratio | 2.08 (25) | 1.02 (26)*** | 0.49 (0.40–0.59) | |
| M-III | Cmax (ng/ml) | 83.7 (37) | 48.8 (31)** | 0.58 (0.46-0.74) |
| tmax (h) | 12 (9.0–24) | 24 (12–24)** | ||
| t1/2 (h) | 22 (19) | 40 (60)* | 1.84 (1.36–2.48) | |
| AUC0–72h (ng⋅h/ml) | 3150 (40) | 2400 (32)* | 0.76 (0.62-0.93) | |
| AUC0–∞ (ng⋅h/ml) | 3630 (40) | 3820 (50) | 1.05 (0.89–1.24) |
↵* P<0.05 versus placebo, **P<0.005 versus placebo, ***P<0.001 versus placebo