Table 1.
Pharmacokinetic variables of a single 4-mg oral dose of rosiglitazone and N-desmethylrosiglitazone in relation to the SLCO1B1 521T→C (Val174Ala) single nucleotide polymorphism
| 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) | |
|---|---|---|---|---|---|
| Rosiglitazone | |||||
| Cmax (ng ml−1) | 361 ± 91 | 353 ± 48 | 1.00 (0.83, 1.21) | 341 ± 99 | 0.94 (0.49, 1.80) |
| AUC0−48 (ng ml−1 h) | 2022 ± 559 | 1763 ± 288 | 0.89 (0.72, 1.11) | 1729 ± 346 | 0.87 (0.63, 1.20) |
| AUC0–∞ (ng ml−1 h) | 2024 ± 561 | 1763 ± 288 | 0.89 (0.72, 1.11) | 1729 ± 346 | 0.87 (0.63, 1.20) |
| Weight-adjusted AUC0–∞ (ng ml−1 h) | 2067 ± 539 | 1693 ± 243 | 0.84 (0.69, 1.01) | 1877 ± 230 | 0.93 (0.71, 1.22) |
| tmax (h) | 1.0 (0.5–2.0) | 1.0 (0.5–1.0) | 1.0 (1.0–1.5) | ||
| t1/2 (h) | 4.1 ± 0.8 | 3.7 ± 0.5 | −0.3 (−1.0, 0.3) | 3.6 ± 0.1 | −0.4 (−1.3, 0.5) |
| N-desmethylrosiglitazone | |||||
| Cmax (U ml−1) | 35.6 ± 4.6 | 35.3 ± 4.7 | 0.99 (0.87, 1.13) | 31.8 ± 5.0 | 0.89 (0.74, 1.10) |
| AUC0−48 (U ml−1 h) | 950 ± 176 | 906 ± 130 | 0.96 (0.82, 1.13) | 836 ± 136 | 0.89 (0.70, 1.13) |
| AUC0–∞ (U ml−1 h) | 1147 ± 263 | 1032 ± 182 | 0.91 (0.75, 1.11) | 958 ± 160 | 0.85 (0.64, 1.13) |
| Weight-adjusted AUC0–∞ (U ml−1 h) | 1166 ± 216 | 994 ± 168 | 0.85 (0.73, 1.00) | 1046 ± 135 | 0.90 (0.72, 1.14) |
| kf | 0.32 ± 0.10 | 0.41 ± 0.21 | 0.09 (−0.09, 0.26) | 0.25 ± 0.03 | −0.08 (−0.15, −0.00) |
| tmax (h) | 8.0 (5.0–12.0) | 8.0 (4.0–12.0) | 12.0 (9.0–12.0) | ||
| t1/2 (h) | 16.9 ± 3.4 | 14.4 ± 2.4 | −2.5 (−5.3, 0.2) | 14.6 ± 1.5 | −2.3 (−6.3, 1.7) |
Data are given as mean ± SD, tmax data as median (range). CI, Confidence interval; Cmax, peak plasma concentration; AUC0−48, area under the plasma concentration–time curve from 0 to 48 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.