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Cited by 349

The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.

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

Open access
Krishna, Gopal, Moton, Allen, Ma, Lei, Medlock, Matthew M., McLeod, James·2009·Antimicrobial Agents and Chemotherapy

Abstract

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.

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Crossref · 10.1128/aac.01034-08

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Metadata

Authors
Krishna, G., Moton, A., Ma, L., Medlock, M. M., & McLeod, J.
Venue
Antimicrobial Agents and Chemotherapy
Published
2009-03
Volume
53
Issue
3
Pages
958-966
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
OpenAlex
W2117813373
Cited by
349
References
39
FWCI
19.86
Type
journal article
Language
en
Open access
green

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