Pharmacokinetics of Posaconazole Administered Orally or by Nasogastric Tube in Healthy Volunteers

Abstract

The use of a nasogastric tube is one means of administering antifungal therapy to critically ill patients unable to receive medication via the oral route. This was a phase 1, open-label, single-center, randomized, crossover study of posaconazole administered via nasogastric tube in healthy volunteers. Each subject received two 400-mg single doses of posaconazole, one administered orally and one administered by nasogastric tube, with a 7-day washout period between each dose. Posaconazole was administered 5 to 10 min after subjects received a nutritional supplement. Blood samples for pharmacokinetic analysis were obtained up to 120 h postdose. The analysis of variance estimate of the study population suggests that the posaconazole nasogastric tube administration least-square mean values of observed maximum concentration (C max ), area under the plasma concentration-time curve (AUC) to the last measurable concentration, and AUC to time infinity were 81%, 76%, and 77%, respectively, of the corresponding oral administration values. The reason for lower C max and AUC values when posaconazole is administered via the nasogastric tube route is not known. Oral and nasogastric tube administration of a single 400-mg dose of posaconazole suspension was safe and well tolerated in healthy adult subjects. The incidence and nature of treatment-emergent adverse events were similar with both administration routes, and no serious adverse events or clinically significant laboratory test or vital sign abnormalities were reported. Obtaining plasma posaconazole concentrations may be warranted when posaconazole is given to patients via a nasogastric tube to ensure adequate posaconazole exposure. Strategies that have been shown to enhance posaconazole exposure (such as splitting the dose and minimizing the use of proton pump inhibitors) may also be used.

Understanding Variability in Posaconazole Exposure Using an Integrated Population Pharmacokinetic Analysis

“…A study in healthy volunteers demonstrated a 24% reduction in posaconazole area under the plasma concentration-time curve when administered via NG tube (40), with clinical studies in patients also confirming a significant reduction in posaconazole exposure (7,41). The lack of significance of this covariate in the present study is likely due to the small number of patients who received posaconazole via NG tube in this analysis (n ϭ 8).…”

Antifungal Susceptibility Patterns of Opportunistic Fungi in the Genera Verruconis and Ochroconis

“…In Fig. 1 33. The widest ranges were seen for FLC (range, 1 to Ն64 g/ml) and 5FC (range, 0.5 to 64 g/ml).…”

“…The triazole POS is an expanded-spectrum triazole with fungicidal activity against a wide spectrum of molds, including Aspergillus species and members of the Mucorales, as well as enhanced activity against Candida and other yeasts (33). The echinocandins represent the newest class of antifungals that exhibit fungicidal activity against many Candida species, making this drug class a desirable alternative to the azole agents, which exhibit only static activity against yeasts.…”

“…The echinocandins represent the newest class of antifungals that exhibit fungicidal activity against many Candida species, making this drug class a desirable alternative to the azole agents, which exhibit only static activity against yeasts. Because mammalian cells have no cell wall, the echinocandins have very few adverse effects in humans (33).…”

Posaconazole Serum Concentrations among Cardiothoracic Transplant Recipients: Factors Impacting Trough Levels and Correlation with Clinical Response to Therapy

“…NS, not significant. ) and AUC values that were only 80% of those observed after oral administration (6). Third, lung transplantation is increasingly offered to older patients.…”