Effects of Varying Amounts of a Liquid Nutritional Supplement on the Pharmacokinetics of Posaconazole in Healthy Volunteers

G. Krishna1, L. Ma1, D. Vickery1, X. Yu1, I. Wu1, E. Power2, E. Beresford1, S. Komathy3

Author address: 

1Schering-Plough, KENILWORTH, NJ, USA 2Cubist Pharmaceuticals, LEXINGTON, MA, USA 3PRA International, RALEIGH, NC, USA

Abstract: 

Objective: To evaluate the pharmacokinetics (PK) of posaconazole (POS) when administered with varying amounts of an oral nutritional supplement (Boost Plus® ). Methods: This was a single-dose, crossover, 5-treatment (Trt), 5-fixed sequence study in 30 healthy subjects who were randomized to receive the following Trts: Trt A, POS 400 mg orally (PO) alone under fasting conditions; Trt B, 1 oz Boost Plus followed by POS 400 mg PO; Trt C, 2 oz Boost Plus followed by POS 400 mg PO; Trt D, 4 oz Boost Plus followed by POS 400 mg PO; Trt E, 8 oz Boost Plus followed by POS 400 mg PO. Blood samples were collected at predetermined time points to evaluate the plasma PK of POS. Log-transformed POS PK parameters were analyzed using ANOVA. Results: POS bioavailability increased almost linearly with increasing amounts of the nutritional supplement, Boost Plus (Table). Based on log-transformed data, the relative bioavailability (AUC) of POS was 35% (fasting), 48% (1 oz), 60% (2 oz), and 77% (4 oz), compared with AUC of POS with 8 oz Boost Plus. Compared with fasting conditions, POS AUC and Cmax increased 2.9- and 3.5-fold, respectively, when given with 8 oz Boost Plus. These findings were in agreement with previous results (Sansone-Parsons, et al. Antimicrob Agents Chemother. 2006;50:1881-1883). Boost Plus increased the extent of absorption; however, Tmax was not affected. Conclusion: Following a single-dose administration of 400 mg POS oral suspension, POS bioavailability increased almost linearly with increasing amounts of the nutritional supplement Boost Plus. Relative to administration of 400 mg POS with 8 oz of Boost Plus, POS AUC was 77% with 4 oz of Boost Plus and 35% under fasting conditions.
2009

abstract No: 

P276

Full conference title: 

4th Trends in Medical Mycology
    • TIMM 4th (2012)