Posaconazole oral suspension is an extended-spectrum triazole that should be taken with food to maximize absorption. A new posaconazole tablet formulation has demonstrated improved bioavailability over the oral suspension in healthy adults in a fasting state. This study evaluated the effects of concomitant medications altering gastric pH (antacid, ranitidine, and esomeprazole) and gastric motility (metoclopramide) on the pharmacokinetics of posaconazole tablets. This was a prospective open-label 5-way crossover study in 20 healthy volunteers. In each treatment period, a single 400-mg dose (4 100-mg tablets) of posaconazole was administered alone or with 20 ml antacid (2 g of aluminum hydroxide and 2 g of magnesium hydroxide), ranitidine (150 mg), esomeprazole (40 mg), or metoclopramide (15 mg). There was a ≥10-day washout between treatment periods. Posaconazole exposure, time to maximum concentration of drug in serum (Tmax), and apparent terminal half-life (t1/2) were similar when posaconazole was administered alone or with medications affecting gastric pH and gastric motility. Geometric mean ratios (90% confidence intervals [CIs]) of the area under the concentration-time curve from time zero to infinity (AUC0-inf) (posaconazole with medications affecting gastric pH and gastric motility versus posaconazole alone) were 1.03 (0.88-1.20) with antacid, 0.97 (0.84-1.12) with ranitidine, 1.01 (0.87-1.17) with esomeprazole, and 0.93 (0.79-1.09) with metoclopramide. Geometric mean ratios (90% CIs) of the maximum concentration of drug in serum (Cmax) were 1.06 (0.90-1.26) with antacid, 1.04 (0.88-1.23) with ranitidine, 1.05 (0.89-1.24) with esomeprazole, and 0.86 (0.73-1.02) with metoclopramide. In summary, in healthy volunteers, the pharmacokinetics of a single 400-mg dose of posaconazole tablets was not altered to a clinically meaningful extent when posaconazole was administered alone or with medications affecting gastric pH or gastric motility.
Recommended CitationKraft, Walter K.; Chang, Peter S.; van Iersel, Marlou L P S; Waskin, Hetty; Krishna, Gopal; and Kersemaekers, Wendy M, "Posaconazole Tablet Pharmacokinetics: Lack of Effect of Concomitant Medications Altering Gastric pH and Gastric Motility in Healthy Subjects." (2014). Department of Pharmacology and Experimental Therapeutics Faculty Papers. Paper 52.