Pharmacokinetics of Posaconazole Coadministered with Antacid in Fasting or Nonfasting Healthy Men

Abstract

Posaconazole is a potent broad-spectrum azole antifungal agent in clinical development for the treatment of invasive fungal infections. This study evaluated the potential for a pH-dependent pharmacokinetic interaction between posaconazole and an antacid (Mylanta), under fasting and nonfasting conditions. Twelve men completed this randomized, four-period crossover, single-dose study. Subjects received 200 mg of posaconazole following a 10-h fast, with 20 ml of Mylanta and a 10-h fast, with 20 ml of Mylanta and a high-fat breakfast, and with a high-fat breakfast alone. Antacid coadministration had no statistically significant effects on posaconazole bioavailability under fasting or nonfasting conditions. In the fasting state, antacid slightly increased the relative oral bioavailability of posaconazole by 15% (P ‫؍‬ 0.296); in the nonfasting state, antacid decreased the relative bioavailability of posaconazole by 12% (P ‫؍‬ 0.352). Food increased the relative oral bioavailability of posaconazole by 400% (P ‫؍‬ 0.001). In conclusion, the effect of antacid on posaconazole exposure in the fasting or nonfasting state was small and is not considered clinically significant.

AspergillusInfections in Transplant Recipients

“…It is orally bioavailable and exhibits doseproportional pharmacokinetics up to a total dose of 800 mg/ day; i.e., saturation of absorption occurs at doses of above 800 mg (61). Food increases the relative oral bioavailability of posaconazole by 400% (62). The drug is metabolized by glucoronidation, with only minor amounts of the unchanged drug excreted in the urine (158).…”

“…Posaconazole is a new triazole compound that exhibits significant in vitro activity against a number of fungi, including Aspergillus (61,62). The drug is currently in advanced stages of clinical development.…”

A routine method for the quantification of the novel antimycotic drug posaconazole in plasma using liquid chromatography-tandem mass spectrometry

“…Posaconazole is available only as an oral suspension, but its absorption appears to be superior to that of itraconazole. However, absorption is greatly influenced by the dosing regimen that is used; for example, twice vs. four times a day dosing for treatment of invasive fungal infections, three times a day dosing for antifungal prophylaxis, or the effect of fat content of concomitant meals (8,9). Typical steady state predose concentrations, maximum concentrations and average concentrations of posaconazole are approximately between 200 and 900 mg/L (10).…”

Optimizing antifungal choice and administration

“…Food also increases the bioavailability of the capsule form 34 . Wide interpatient pharmacokinetic variability has also been observed with posaconazole 35 , and similar to itraconazole, absorption and bioavailability of posaconazole is markedly increased when administered with food or a nutritional supplement versus when fasting [36][37][38][39] . Gastric acidity is also important for posaconazole absorption 40 .…”