Effects of Food on the Pharmacokinetics of Irbesartan/Hydrochlorothiazide Combination Tablet

Objective: The effects of food on the pharmacokinetics of an irbesartan/ hydrochlorothiazide combination tablet were assessed in 16 healthy young male volunteers. Methods: Each subject received a 150mg/12.5mg irbesartan/hydrochlorothiazide tablet following an overnight (approximately 10 hours) fast or 5 minutes after a high fat breakfast according to a randomisation schedule. Two treatments were separated by at least a 7-day washout period. Serial blood samples were collected over a 72-hour period and plasma samples were analysed for irbesartan and hydrochlorothiazide using validated procedures. Results: No statistically significant effects of food were observed in any of the irbesartan pharmacokinetic parameters analysed, except for the time to peak observed concentration (t max ), which was prolonged from a median of 1.0 hour in the fasted state to 2.0 hours in the fed state. The geometric means for irbesartan eak concentrations (C max ) and area under the plasma concentration-time curve extrapolated to infinity (AUC 0-∞ ) decreased less than 4% under the fed condition compared with the fasted state. The geometric means for hydrochlorothiazide decreased 21 and 8% for C max and AUC 0-∞ , respectively, when the combination tablet was administered with food compared with the fasted state. The decrease in C max was statistically significant. Food also significantly prolonged the median t max , 1.5 hours vs 3.5 hours. However, these changes in the pharmacokinetic parameters were not clinically significant. Conclusion: The combination tablet of irbesartan/hydrochlorothiazide can be administered without regard to meals.