TABLE II

FROM:

Effects of Gemfibrozil, Itraconazole, and Their Combination on the Pharmacokinetics of Pioglitazone

Tiina Jaakkola, Janne T. Backman, Mikko Neuvonen and Pertti J. Neuvonen

Table II. Pharmacokinetic variables of itraconazole, hydroxyitraconazole, and gemfibrozil in plasma in 12 healthy volunteers on days 3 to 5 of a 4-day treatment with 100 mg itraconazole (first dose, 200 mg), 600 mg gemfibrozil, or both gemfibrozil and itraconazole twice daily

Variable	Gemfibrozil phase	Itraconazole phase	Itraconazole plus gemfibrozil phase
Itraconazole
Cmax (mg/L)		306 72	159 65*
% of itraconazole phase and range		100%	52% (27%–72%)
C48 (mg/L)		248 90	130 97†
% of itraconazole phase and range		100%	52% (9%–92%)
AUC(0–10) (mg h/L)		2264 449	1200 486*
% of itraconazole phase and range		100%	53% (32%–77%)
AUC(0–49) (mg h/L)		11,650 4090	6263 3481*
% of itraconazole phase and range		100%	54% (25%–81%)
Hydroxyitraconazole
Cmax (mg/L)		596 98	357 102*
% of itraconazole phase and range		100%	60% (33%–83%)
C48 (mg/L)		703 184	339 238†
% of itraconazole phase and range		100%	48% (4%–101%)
AUC(0–10) (mg h/L)		5270 736	3110 911*
% of itraconazole phase and range		100%	59% (33%–283%)
AUC(0–49) (mg h/L)		29,330 5305	15,750 7455*
% of itraconazole phase and range		100%	54% (23%–93%)
Hydroxyitraconazole-to-itraconazole AUC(0–49) ratio		2.66 0.53	2.62 0.39
% of itraconazole phase and range		100%	98% (73%–131%)
Gemfibrozil
Cmax (mg/L)	30.6 9.6		31.2 9.6
C48 (mg/L)	1.6 0.8		1.8 1.4
AUC(0–10) (mg h/L)	118.3 53.4		116.2 40.3
AUC(0–49) (mg h/L)	681.0 405.1		761.3 307.1

 Data are given as mean SD or as percent and range.

 C_max, Observed peak plasma concentration from time 0 to 10 hours (9 hours after pioglitazone intake); C₄₈, concentration at 48 hours after pioglitazone intake; AUC(0–10), area under concentration versus time curve to 10 hours; AUC(0–49), area under concentration versus time curve to 49 hours.

^*  P <.001, versus itraconazole phase.

^†  P <.01, versus itraconazole phase.