Table 2.
Pharmacokinetic variables of a single 15-mg oral dose of pioglitazone and its metabolites in relation to the SLCO1B1 521T→C (Val174Ala) single nucleotide poymorphism
| c.521TT (n = 16) | c.521TC (n = 12) | Mean ratio/difference c.521TC vs. c.521TT* (95% CI) | c.521CC (n = 4) | Mean ratio/difference c.521CC vs. c.521TT* (95% CI) | |
|---|---|---|---|---|---|
| Pioglitazone | |||||
| Cmax (ng ml−1) | 617 ± 129 | 610 ± 205 | 0.95 (0.73, 1.25) | 590 ± 165 | 0.95 (0.64, 1.42) |
| AUC0−72 (ng ml−1 h) | 6228 ± 1892 | 5117 ± 1165 | 0.83 (0.65, 1.06) | 4850 ± 1121 | 0.80 (0.55, 1.14) |
| AUC0–∞ (ng ml−1 h) | 6244 ± 1909 | 5123 ± 1165 | 0.83 (0.65, 1.06) | 4851 ± 1123 | 0.79 (0.55, 1.14) |
| Weight-adjusted AUC0–∞ (ng ml−1 h) | 6422 ± 2050 | 4922 ± 1062 | 0.78 (0.61, 1.00) | 5384 ± 1469 | 0.85 (0.59, 1.22) |
| tmax (h) | 1.8 (1.0–4.0) | 2.0 (1.0–4.0) | 1.3 (1.0–1.5) | ||
| t1/2 (h) | 7.9 ± 2.5 | 7.4 ± 1.5 | −0.5 (−2.4, 1.5) | 6.2 ± 0.5 | −1.7 (−4.5, 1.1) |
| M3 | |||||
| Cmax (ng ml−1) | 86 ± 31 | 84 ± 29 | 0.97 (0.73, 1.29) | 78 ± 16 | 0.93 (0.62, 1.41) |
| AUC0−72 (ng ml−1 h) | 3456 ± 1233 | 3104 ± 792 | 0.92 (0.70, 1.21) | 3210 ± 708 | 0.96 (0.64, 1.43) |
| AUC0–∞ (ng ml−1 h) | 4059 ± 1531 | 3594 ± 871 | 0.92 (0.68, 1.23) | 3649 ± 739 | 0.94 (0.61, 1.45) |
| Weight-adjusted AUC0–∞ (ng ml−1 h) | 4106 ± 1242 | 3457 ± 861 | 0.86 (0.66, 1.12) | 4017 ± 921 | 1.00 (0.68, 1.48) |
| kf | 0.21 ± 0.06 | 0.25 ± 0.11 | 0.04 (−0.04, 0.12) | 0.20 ± 0.06 | −0.02 (−0.13, 0.10) |
| tmax (h) | 12.0 (7.0–24.0) | 12.0 (4.0–24.0) | 12.0 (12.0–24.0) | ||
| t1/2 (h) | 23.2 ± 4.7 | 22.8 ± 4.2 | −0.4 (−4.5, 3.6) | 21.5 ± 1.9 | −1.7 (−7.7, 4.1) |
| M4 | |||||
| Cmax (ng ml−1) | 257 ± 39 | 266 ± 75 | 1.01 (0.83, 1.23) | 223 ± 38 | 0.87 (0.65, 1.16) |
| AUC0−72 (ng ml−1 h) | 10949 ± 1902 | 11061 ± 2745 | 1.00 (0.82, 1.21) | 9577 ± 2192 | 0.87 (0.65, 1.16) |
| AUC0–∞ (ng ml−1 h) | 12890 ± 2433 | 12802 ± 3252 | 0.98 (0.79, 1.21) | 11202 ± 3001 | 0.86 (0.63, 1.78) |
| Weight-adjusted AUC0–∞ (ng ml−1 h) | 13227 ± 2216 | 12307 ± 3096 | 0.92 (0.74, 1.14) | 12451 ± 3807 | 0.92 (0.67, 1.26) |
| kf | 0.18 ± 0.06 | 0.21 ± 0.08 | 0.03 (−0.03, 0.09) | 0.18 ± 0.02 | 0.01 (−0.08, 0.09) |
| tmax (h) | 12.0 (9.0–24.0) | 12.0 (5.0–24.0) | 12.0 (12.0–12.0) | ||
| t1/2 (h) | 24.0 ± 4.0 | 22.6 ± 4.4 | −1.4 (−5.3, 2.5) | 22.7 ± 3.4 | −1.2 (−6.9, 4.5) |
| M5 | |||||
| Cmax (U ml−1) | 32 ± 12 | 42 ± 28 | 1.22 (0.80, 1.85) | 34 ± 15 | 1.05 (0.56, 1.94) |
| AUC0−72 (U ml−1 h) | 568 ± 206 | 623 ± 326 | 1.06 (0.71, 1.58) | 476 ± 186 | 0.85 (0.47, 1.52) |
| AUC0–∞ (U ml−1 h) | 571 ± 208 | 629 ± 325 | 1.06 (0.71, 1.59) | 494 ± 210 | 0.86 (0.49, 1.56) |
| Weight-adjusted AUC0–∞ (ng ml−1 h) | 585 ± 211 | 584 ± 222 | 1.00 (0.69, 1.43) | 535 ± 212 | 0.92 (0.54, 1.57) |
| kf | 0.42 ± 0.13 | 0.46 ± 0.12 | 0.04 (−0.08, 0.15) | 0.72 ± 0.40 | 0.30 (−0.53, 1.13) |
| tmax (h) | 5.0 (3.0–12.0) | 5.0 (4.0–7.0) | 3.0 (1.5–5.0) | ||
| t1/2 (h) | 9.1 ± 1.7 | 8.5 ± 2.1 | −0.6 (−2.5, 1.4) | 8.6 ± 3.1 | −0.5 (−3.3, 2.3) |
Data are given as mean ± SD, tmax data as median (range). CI, Confidence interval; Cmax, peak plasma concentration; AUC0−72, area under the plasma concentration–time curve from 0 to 72 h; AUC0–∞, area under the plasma concentration–time curve from time 0 to infinity; tmax, time to Cmax; t1/2, elimination half-life; kf, apparent formation rate constant.
*
These data are geometric mean ratio (95% CI) for the Cmax and AUC values and mean difference (95% CI) for the t1/2 and kf values.