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Antimicrobial Agents and Chemotherapy, March 2009, p. 958-966, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.01034-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics and Absorption of Posaconazole Oral Suspension under Various Gastric Conditions in Healthy Volunteers {triangledown}

Gopal Krishna,1* Allen Moton,1 Lei Ma,1 Matthew M. Medlock,2 and James McLeod1

Early Clinical Research and Experimental Medicine, Schering-Plough Research Institute, Kenilworth, New Jersey,1 PPD Development LP, Austin, Texas2

Received 1 August 2008/ Returned for modification 18 October 2008/ Accepted 9 December 2008

A four-part, randomized, crossover study with healthy subjects evaluated the effects of gastric pH, the dosing frequency and prandial state, food consumption timing, and gastric motility on the absorption of posaconazole. In part 1, a single dose (SD) of posaconazole (400 mg) was administered alone or with an acidic beverage or a proton pump inhibitor (PPI), or both. In part 2, posaconazole (400 mg twice daily and 200 mg four times daily) was administered for 7 days with and without a nutritional supplement (Boost). In part 3, an SD of posaconazole (400 mg) was administered while the subjects were fasting and before, during, and after a high-fat meal. In part 4, an SD of posaconazole (400 mg) and the nutritional supplement were administered alone, with metoclopramide, and with loperamide. Compared to the results obtained with posaconazole alone, administration with an acidic beverage increased the posaconazole maximum concentration in plasma (Cmax) and the area under the concentration-time curve (AUC) by 92% and 70%, respectively, whereas a higher gastric pH decreased the posaconazole Cmax and AUC by 46% and 32%, respectively. Compared to the results obtained with posaconazole alone, posaconazole at 400 mg or at 200 mg plus the nutritional supplement increased the posaconazole Cmax and AUC by 65% and 66%, respectively, and by up to 137% and 161%, respectively. Administration before a high-fat meal increased the Cmax and the AUC by 96% and 111%, respectively, while administration during and after the meal increased the Cmax and the AUC by up to 339% and 387%, respectively. Increased gastric motility decreased the Cmax and the AUC by 21% and 19%, respectively. Strategies to maximize posaconazole exposure in patients with absorption difficulties include administration with or after a high-fat meal, with any meal or nutritional supplement, with an acidic beverage, or in divided doses and the avoidance of proton pump inhibitors.

* Corresponding author. Mailing address: Schering-Plough Research Institute, 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 15 December 2008.

Antimicrobial Agents and Chemotherapy, March 2009, p. 958-966, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.01034-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Pea, F., Furlanut, M., Viale, P., Krishna, G., Moton, A., Ma, L., McLeod, J., Medlock, M. M. (2009). What Should Be the First-Choice Strategy To Maximize Posaconazole Exposure in Daily Clinical Practice?. Antimicrob. Agents Chemother. 53: 3608-3610 [Full Text]  
  • Dodds Ashley, E. S., Varkey, J. B., Krishna, G., Vickery, D., Ma, L., Yu, X., Malavade, D., Goodwin, M., Perfect, J. R., Power, E. (2009). Pharmacokinetics of Posaconazole Administered Orally or by Nasogastric Tube in Healthy Volunteers. Antimicrob. Agents Chemother. 53: 2960-2964 [Abstract] [Full Text]  
  • Thompson, G. R. III, Rinaldi, M. G., Pennick, G., Dorsey, S. A., Patterson, T. F., Lewis, J. S. II (2009). Posaconazole Therapeutic Drug Monitoring: a Reference Laboratory Experience. Antimicrob. Agents Chemother. 53: 2223-2224 [Full Text]  


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