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Antimicrobial Agents and Chemotherapy, July 2009, p. 2960-2964, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.01178-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

Elizabeth S. Dodds Ashley,1 Jay B. Varkey,1 Gopal Krishna,2* Donna Vickery,2 Lei Ma,2 Xin Yu,2 Darshana Malavade,2 Megan Goodwin,1 John R. Perfect,1 and Eddie Power2

Duke University Medical Center, Durham, North Carolina,1 Schering-Plough Research Institute, Kenilworth, New Jersey2

Received 4 September 2008/ Returned for modification 6 January 2009/ Accepted 4 May 2009

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 (Cmax), 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 Cmax 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.

* Corresponding author. Mailing address: Early Clinical Research and Experimental Medicine, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033. Phone and fax: (908) 740-6564. E-mail: gopal.krishna{at}spcorp.com

{triangledown} Published ahead of print on 11 May 2009.

Antimicrobial Agents and Chemotherapy, July 2009, p. 2960-2964, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.01178-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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