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Antimicrobial Agents and Chemotherapy, November 2009, p. 4749-4752, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00889-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Effect of Varying Amounts of a Liquid Nutritional Supplement on the Pharmacokinetics of Posaconazole in Healthy Volunteers{triangledown}

Gopal Krishna,1* Lei Ma,1 Donna Vickery,1,{dagger} Xin Yu,1 Irene Wu,1 Edward Power,1,{ddagger} Eric Beresford,1 and Steven Komjathy2

Schering-Plough, Kenilworth, New Jersey,1 PRA International, Lenexa, Kansas2

Received 30 June 2009/ Returned for modification 4 August 2009/ Accepted 1 September 2009

The aim of this single-center, phase 1, randomized, 5 by 5 crossover, open-label study was to determine the effects of varying amounts of a nutritional supplement (Boost Plus) on the pharmacokinetics of posaconazole in 30 healthy volunteers. After an overnight fast, subjects were administered a single dose of 400 mg posaconazole oral suspension alone or following Boost Plus (8 fluid ounces [oz] [240 ml], 4 oz [120 ml], 2 oz [60 ml], or 1 oz [30 ml]). Subjects were randomized to receive all five treatments in different sequences, with a 14-day washout between treatments. Primary pharmacokinetic variables—area under the concentration-time curve from time zero to the time of the final quantifiable sample (AUCtf), maximum observed plasma concentration (Cmax), time to Cmax (Tmax), and relative bioavailability—were assessed up to 5 days postdose. Safety assessments included testing for adverse events, clinical laboratory tests, measurement of vital signs, physical examinations, and electrocardiograms. Posaconazole bioavailability increased almost linearly with increasing amounts of Boost Plus. Based on log-transformed data, the relative bioavailabilities (AUCs) of posaconazole were 35% (fasting), 48% (1 oz), 60% (2 oz), and 77% (4 oz) of the level reached in the presence of 8 oz Boost Plus, whereas Tmax was unaffected. Compared with the levels reached under fasting conditions, posaconazole Cmax and AUC values increased 3.5- and 2.9-fold, respectively, when given with 8 oz Boost Plus. Single doses of posaconazole at 400 mg alone and with 1, 2, 4, or 8 oz Boost Plus were safe and well tolerated in healthy subjects.

* Corresponding author. Mailing address: Schering-Plough Research Institute, K15-2-2650, 2015 Galloping Hill Road, Kenilworth, NJ 07033. Phone: (908) 740-6564. Fax: (908) 740-2916. E-mail: gopal.krishna{at}spcorp.com

{triangledown} Published ahead of print on 8 September 2009.

{dagger} Present address: Forest Research Institute, Jersey City, NJ 07311.

{ddagger} Present address: Cubist Pharmaceuticals, Lexington, MA 02421.

Antimicrobial Agents and Chemotherapy, November 2009, p. 4749-4752, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00889-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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