TABLE I
FROM:
Effects of Gemfibrozil, Itraconazole, and Their Combination on the Pharmacokinetics of Pioglitazone
Tiina Jaakkola, Janne T. Backman, Mikko Neuvonen and Pertti J. Neuvonen
BACK TO ARTICLETable I. Pharmacokinetic variables of pioglitazone in 12 healthy volunteers after a single oral dose of 15 mg pioglitazone on day 3 of a 4-day treatment with 600 mg gemfibrozil, 100 mg itraconazole (first dose, 200 mg), both gemfibrozil and itraconazole, or placebo twice daily
| Variable | Placebo phase (control) | Gemfibrozil phase | Itraconazole phase | Itraconazole plus gemfibrozil phase |
|---|---|---|---|---|
| Pioglitazone | ||||
| Cmax (ng/mL) | 518  224 | 547 213 | 544 228 | 390 136 |
| % of control and range | 100% | 106% (52%–260%) | 105% (68%–185%) | 75% (35%–173%) |
| tmax (h) | 2 (1–4) | 3 (1–7) | 1.5 (1–5) | 3 (1–12) |
| t½ (h) | 8.3 2.2 | 22.7 7.6*
†
| 8.7 2.6 | 40.0 34.8*
†
|
| % of control and range | 100% | 274% (153%–553%) | 105% (56%–151%) | 483% (170%–1663%) |
AUC(0–48) (mg  h/L) | 5.14 2.30 | 12.88 4.31*
†
| 5.56 3.02 | 11.07 3.26*
†
|
| % of control and range | 100% | 250% (153%–552%) | 108% (76%–160%) | 215% (137%–488%) |
AUC(0- ) (mg h/L) | 5.25 2.33 | 16.91 5.47*
†
| 5.73 3.15 | 20.50 14.79*
†
|
| % of control and range | 100% | 322% (227%–653%) | 109% (77%–157%) | 391% (220%–867%) |
| M-III | ||||
| Cmax (U/mL) | 0.23 0.08 | 0.13 0.04*
†
| 0.25 0.08 | 0.12 0.04*
†
|
| % of control and range | 100% | 55% (35%–96%) | 106% (81%–154%) | 51% (32%–105%) |
| tmax (h) | 12 (7–24) | 24 (24–48)‡ | 24 (7–24) | 48 (24–48)‡ § |
| t½ (h) | 35.2 14.1 | NE
| 38.7 26.3 | NE
|
| % of control and range | 100% | — | 110% (43–297%) | — |
| AUC(0–48) (U h/mL) | 8.18 2.78 | 4.73 1.50‡
§
| 8.78 2.91 | 4.14 1.61*
†
|
| % of control and range | 100% | 58% (30%–96%) | 107% (83%–129%) | 51% (24%–112%) |
| AUC(0-) (U h/mL) | 14.53 6.24 | NE
| 18.93 17.41 | NE
|
| % of control and range | 100% | — | 130% (68%–266%) | — |
| M-IV | ||||
| Cmax (U/mL) | 0.42 0.11 | 0.22 0.05*
†
| 0.41 0.10 | 0.20 0.05*
†
|
| % of control and range | 100% | 51% (33%–74%) | 98% (80%–145%) | 48% (32%–97%) |
| tmax (h) | 12 (12–24) | 24 (24–48)‡ § | 12 (9–24) | 48 (24–48)‡ § |
| t½ (h) | 32.7 14.1 | NE
| 37.1 14.7 | NE
|
| % of control and range | 100% | — | 114% (65–259%) | — |
| AUC(0–48) (U h/mL) | 14.44 3.92 | 7.90 2.02*
†
| 14.18 3.63 | 7.01 1.98*
†
|
| % of control and range | 100% | 55% (31%–95%) | 98% (76%–138%) | 49% (24%–107%) |
| AUC(0-) (U h/mL) | 24.75 10.67 | NE
| 26.43 11.98 | NE
|
| % of control and range | 100% | — | 107% (77%–202%) | — |
Data are given as mean SD, except for tmax data, which are given as median and range.
Cmax, Observed peak plasma concentration; tmax, time to reach peak plasma concentration; t½, elimination half-life; AUC(0–48), area under concentration versus time curve to 48 hours; AUC(0-), area under concentration versus time curve to infinity; NE, not estimated.
* Bonferroni-adjusted P value: P < .001, versus placebo phase.
† Bonferroni-adjusted P value: P < .001, versus itraconazole phase.
‡ Bonferroni-adjusted P value: P < .05, versus placebo phase.
§ Bonferroni-adjusted P value: P < .05, versus itraconazole phase.
The t½ and AUC(0-) values of M-III and M-IV could not be estimated during the gemfibrozil and gemfibrozil-itraconazole phases.
