Poster presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy (52nd ICAAC) held in San Francisco 9/9-9/12
Background: Posaconazole (POS) oral suspension is an extended-spectrum triazole that should be taken with food to maximize absorption. A new POS tablet formulation has demonstrated improved bioavailability over oral suspension in healthy adults in the fasting state. This study evaluated the effect of concomitant medications altering gastric pH (antacid, ranitidine, and esomeprazole) and motility (metoclopramide) on the pharmacokinetics of POS tablet.
Methods: This was a prospective, open-label, 5-way crossover study in 20 healthy volunteers. In each treatment period, a single 400-mg (100 mg x 4) dose of POS tablets was administered alone or with 20 mL antacid (Mylanta® Ultimate Strength Liquid, aluminum hydroxide 2 g and magnesium hydroxide 2 g), ranitidine (150 mg), esomeprazole (40 mg), or metoclopramide (15 mg). There was ≥10-day washout between treatment periods.
Results: POS exposure, Tmax, and t½ were similar when administered alone or with medications affecting gastric pH and motility. Geometric mean ratios (90% CI) of AUC0-last compared with those of POS alone were antacid, 1.04 (0.90–1.20); ranitidine, 0.97 (0.84–1.12); esomeprazole, 1.02 (0.88–1.17); and metoclopramide, 0.93 (0.80–1.07). Geometric mean ratios (90% CI) of Cmax compared with those of POS alone were antacid, 1.06 (0.90–1.26); ranitidine, 1.04 (0.88–1.23); esomeprazole, 1.05 (0.89–1.24); and metoclopramide, 0.86 (0.73–1.02).
Conclusions: In healthy volunteers, the pharmacokinetics of a single dose of POS tablet 400 mg were similar when administered alone or with medications affecting gastric pH or motility.
Recommended CitationKraft, Walter K.; Chang, P.; Van Iersel, MLPS; Waskin, H.; Krishna, G.; and Kersemaekers, W., "Effect of Concomitant Medications Affecting Gastric pH and Motility on Posaconazole Tablet Pharmacokinetics" (2012). Department of Pharmacology and Experimental Therapeutics Faculty Papers. Paper 37.