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Novel nanocrystal formulation of megestrol acetate has improved bioavailability compared with the conventional micronized formulation in the fasting state
BACKGROUND: Megestrol acetate is an effective treatment for improving appetite and increasing body weight in patients with cancer-associated anorexia. However, Megace(®) oral suspension (OS), a micronized formulation of megestrol acetate, has low bioavailability in the fasting state. To overcome thi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077389/ https://www.ncbi.nlm.nih.gov/pubmed/25028536 http://dx.doi.org/10.2147/DDDT.S62176 |
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author | Jang, Kyungho Yoon, Seonghae Kim, Sung-Eun Cho, Joo-Youn Yoon, Seo Hyun Lim, Kyoung Soo Yu, Kyung-Sang Jang, In-Jin Lee, Howard |
author_facet | Jang, Kyungho Yoon, Seonghae Kim, Sung-Eun Cho, Joo-Youn Yoon, Seo Hyun Lim, Kyoung Soo Yu, Kyung-Sang Jang, In-Jin Lee, Howard |
author_sort | Jang, Kyungho |
collection | PubMed |
description | BACKGROUND: Megestrol acetate is an effective treatment for improving appetite and increasing body weight in patients with cancer-associated anorexia. However, Megace(®) oral suspension (OS), a micronized formulation of megestrol acetate, has low bioavailability in the fasting state. To overcome this limitation, a nanocrystal formulation has been developed. This study was performed to evaluate the pharmacokinetics and tolerability of the nanocrystal formulation and to compare them with those of Megace(®) OS in the fed and fasting states. METHODS: A randomized, open-label, two-treatment, two-period, two-sequence, crossover study was performed in three parts in 93 healthy subjects. A single 625 mg/5 mL oral dose of a nanocrystal formulation was administered in the fasting and fed states (part I). In parts II and III, a single 625 mg/5 mL oral dose of the nanocrystal formulation or Megace(®) OS 800 mg/20 mL was given in the fed and fasting states, respectively. Blood samples were collected for up to 120 hours post dose for pharmacokinetic analysis. Tolerability was evaluated throughout the entire study period. RESULTS: The nanocrystal formulation of megestrol acetate was rapidly absorbed in both the fed and fasting states. In the fed state, systemic exposure was comparable between the nanocrystal formulation of megestrol acetate and Megace(®) OS. In the fasting state, however, the peak plasma concentration and area under the plasma concentration-time curve to the last measurable concentration of megestrol acetate was 6.7-fold and 1.9-fold higher, respectively, for the nanocrystal formulation than for Megace(®) OS. No serious adverse events were reported. CONCLUSION: Systemic exposure to megestrol acetate is less affected by lack of concomitant food intake when it is administered using the nanocrystal formulation. The nanocrystal formulation of megestrol acetate could be more effective in treating patients with cachexia or anorexia. |
format | Online Article Text |
id | pubmed-4077389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40773892014-07-15 Novel nanocrystal formulation of megestrol acetate has improved bioavailability compared with the conventional micronized formulation in the fasting state Jang, Kyungho Yoon, Seonghae Kim, Sung-Eun Cho, Joo-Youn Yoon, Seo Hyun Lim, Kyoung Soo Yu, Kyung-Sang Jang, In-Jin Lee, Howard Drug Des Devel Ther Original Research BACKGROUND: Megestrol acetate is an effective treatment for improving appetite and increasing body weight in patients with cancer-associated anorexia. However, Megace(®) oral suspension (OS), a micronized formulation of megestrol acetate, has low bioavailability in the fasting state. To overcome this limitation, a nanocrystal formulation has been developed. This study was performed to evaluate the pharmacokinetics and tolerability of the nanocrystal formulation and to compare them with those of Megace(®) OS in the fed and fasting states. METHODS: A randomized, open-label, two-treatment, two-period, two-sequence, crossover study was performed in three parts in 93 healthy subjects. A single 625 mg/5 mL oral dose of a nanocrystal formulation was administered in the fasting and fed states (part I). In parts II and III, a single 625 mg/5 mL oral dose of the nanocrystal formulation or Megace(®) OS 800 mg/20 mL was given in the fed and fasting states, respectively. Blood samples were collected for up to 120 hours post dose for pharmacokinetic analysis. Tolerability was evaluated throughout the entire study period. RESULTS: The nanocrystal formulation of megestrol acetate was rapidly absorbed in both the fed and fasting states. In the fed state, systemic exposure was comparable between the nanocrystal formulation of megestrol acetate and Megace(®) OS. In the fasting state, however, the peak plasma concentration and area under the plasma concentration-time curve to the last measurable concentration of megestrol acetate was 6.7-fold and 1.9-fold higher, respectively, for the nanocrystal formulation than for Megace(®) OS. No serious adverse events were reported. CONCLUSION: Systemic exposure to megestrol acetate is less affected by lack of concomitant food intake when it is administered using the nanocrystal formulation. The nanocrystal formulation of megestrol acetate could be more effective in treating patients with cachexia or anorexia. Dove Medical Press 2014-06-25 /pmc/articles/PMC4077389/ /pubmed/25028536 http://dx.doi.org/10.2147/DDDT.S62176 Text en © 2014 Jang et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Jang, Kyungho Yoon, Seonghae Kim, Sung-Eun Cho, Joo-Youn Yoon, Seo Hyun Lim, Kyoung Soo Yu, Kyung-Sang Jang, In-Jin Lee, Howard Novel nanocrystal formulation of megestrol acetate has improved bioavailability compared with the conventional micronized formulation in the fasting state |
title | Novel nanocrystal formulation of megestrol acetate has improved bioavailability compared with the conventional micronized formulation in the fasting state |
title_full | Novel nanocrystal formulation of megestrol acetate has improved bioavailability compared with the conventional micronized formulation in the fasting state |
title_fullStr | Novel nanocrystal formulation of megestrol acetate has improved bioavailability compared with the conventional micronized formulation in the fasting state |
title_full_unstemmed | Novel nanocrystal formulation of megestrol acetate has improved bioavailability compared with the conventional micronized formulation in the fasting state |
title_short | Novel nanocrystal formulation of megestrol acetate has improved bioavailability compared with the conventional micronized formulation in the fasting state |
title_sort | novel nanocrystal formulation of megestrol acetate has improved bioavailability compared with the conventional micronized formulation in the fasting state |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077389/ https://www.ncbi.nlm.nih.gov/pubmed/25028536 http://dx.doi.org/10.2147/DDDT.S62176 |
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