TABLE 2

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