The Effect of a Nutritional Supplement (Boost Plus) on the Oral Bioavailability of Posaconazole.

R. COURTNEY, A. SANSONE, A. CALZETTA, M. MARTINHO, M. LAUGHLIN

Author address: 

Schering-Plough Research Institute, Kenilworth, NJ.

Abstract: 

Background: Many patients who require antifungal therapy receive nutritional supplements via a nasogastric tube. This pharmacokinetic (PK) study was conducted to determine the effect of a nutritional supplement (Boost Plus) on the systemic exposure to posaconazole (POS), a potent broad-spectrum triazole antifungal agent. Methods: Twenty-four healthy adult volunteers were enrolled in this open-label, randomized, crossover study. Subjects received a single 400-mg dose of POS oral suspension while fasted or with 8 fl oz of Boost Plus (360 Calories) on Day 1. Following a 14-day washout, the alternate treatment was administered on Day 15 in a crossover manner. Blood samples were collected predose and up to 72 hrs postdose. PK parameters were calculated using model-independent methods and statistically analyzed using an analysis of variance model. Results: The administration of Boost Plus increased the extent but not rate of POS absorption. Based on point estimates and 90% confidence intervals, POS concentrations (Cmax and AUC(tf)) were 3.4- and 2.6-fold greater, respectively, when POS was administered with Boost Plus relative to administration of POS under fasted conditions. However, Boost Plus had no statistically significant effect on the mean time to Cmax (4.83 hr for POS alone vs 5.48 hr for POS + Boost). POS was well tolerated under both conditions. Parameter Point Estimate 90% Confidence Interval P value (%) Cmax 335a 275-408 0.001 AUC(0 - tf) 263a 227-306 0.001 a Ratio of POS + Boost Plus to POS alone. Conclusions: Coadministration of POS suspension and Boost Plus resulted in a statistically significant and marked increase in systemic exposure to oral POS. These results suggest that, for patients who are unable to eat solid foods, POS should be administered with a nutritional supplement whenever possible.
2003

abstract No: 

A-1604

Full conference title: 

43rd Interscience Conference on Antimicrobial Agents
    • ICAAC 43rd