Pharmacokinetic variables of pioglitazone after a single oral dose of 15 mg of pioglitazone on day 3 of a 6-day treatment with placebo or 160 mg trimethoprim twice daily in subjects with the CYP2C8*1/*1 genotype (n = 8), CYP2C8*1/*3 genotype (n = 5), and CYP2C8*3/*3 genotype (n = 3) Values are mean ± S.D., unless otherwise indicated.
Variable | Placebo Phase (Control)a | Trimethoprim Phasea | Trimethoprim Phase, % of Controlb | p between Phasesc | p between Genotypesc |
---|---|---|---|---|---|
Cmax (ng/ml) | |||||
*1/*1 | 597 ± 115 | 659 ± 173 | 110 (65–183) | ||
*1/*3 | 566 ± 123 | 707 ± 159 | 125 (93–233) | ||
*3/*3 | 511 ± 213 | 593 ± 169 | 116 (89–179) | ||
Mean | 571 ± 131 | 662 ± 162 | 116 (65–233) | 0.104 | 0.476 |
t1/2 (h) | |||||
*1/*1 | 4.5 ± 0.6 | 5.6 ± 1.4 | 126 (98–182) | ||
*1/*3 | 3.4 ± 0.5* | 4.7 ± 1.3 | 140 (111–159) | ||
*3/*3 | 3.3 ± 0.3* | 4.5 ± 0.9 | 139 (110–176) | ||
Mean | 3.9 ± 0.8 | 5.1 ± 1.3 | 132 (98–182) | <0.001 | 0.070 |
AUC0–∞ (mg · h/l) | |||||
*1/*1 | 5.02 ± 1.07 | 6.88 ± 2.27 | 137 (81–164) | ||
*1/*3 | 3.87 ± 1.15 | 6.00 ± 1.99 | 155 (101–228) | ||
*3/*3 | 3.70 ± 1.19 | 5.18 ± 1.66 | 140 (97–200) | ||
Mean | 4.42 ± 1.21 | 6.29 ± 2.07 | 142 (81–228) | <0.001 | 0.192 |
Cmax, adj (ng/ml) | |||||
*1/*1 | 592 ± 135 | 635 ± 96 | 107 (65–183) | ||
*1/*3 | 542 ± 113 | 667 ± 97 | 123 (93–233) | ||
*3/*3 | 445 ± 163 | 514 ± 25*† | 115 (89–179) | ||
Mean | 549 ± 137 | 622 ± 100 | 113 (65–233) | 0.104 | 0.021 |
AUC0–∞, adj (mg · h/l) | |||||
*1/*1 | 4.95 ± 0.96 | 6.60 ± 1.47 | 133 (81–164) | ||
*1/*3 | 3.67 ± 0.92* | 5.70 ± 1.62 | 155 (101–228) | ||
*3/*3 | 3.25 ± 0.87* | 4.45 ± 0.46* | 137 (97–200) | ||
Mean | 4.23 ± 1.15 | 5.92 ± 1.56 | 140 (81–228) | <0.001 | 0.017 |
Cmax, peak plasma concentration; t1/2, dominant elimination half-life; AUC0–∞, area under the plasma concentration-time curve from time 0 to infinity; Cmax, adj, peak plasma concentration adjusted for 70 kg b.wt.; AUC0–∞, adj, area under the plasma concentration-time curve from time 0 to infinity adjusted for 70 kg b.wt.
↵ a Values are mean ± S.D.
↵ b Values are mean (range)
↵ c p value from repeated-measures ANOVA with genotype as between-subjects factor
↵* p < 0.05 versus *1/*1
↵† p < 0.05 versus *1/*3