{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T05:55:50Z","timestamp":1711691750708},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,11,4]],"date-time":"2016-11-04T00:00:00Z","timestamp":1478217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Brain Korea 21 PLUS Project for Medical Science, Yonsei University"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Megestrol acetate, an appetite stimulant with low bioavailability, shows increased bioavailability when taken together with food. However, the pharmacokinetic characteristics of megestrol acetate and its relation with food are not well understood. This study aimed to investigate the food effect on the pharmacokinetics (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>) of the recently developed nano\u2010crystallized megestrol acetate (<jats:styled-content style=\"fixed-case\">NCMA<\/jats:styled-content>), using a model\u2010based approach. Data were obtained from an <jats:styled-content style=\"fixed-case\">NCMA PK<\/jats:styled-content> study consisting of a single dose in fasting (39 individuals) and fed conditions (40 individuals). Plasma concentrations were measured up to 120 hr after dosing. With the incorporation of body\u2010weight via allometry, <jats:styled-content style=\"fixed-case\">NONMEM<\/jats:styled-content> 7.3 was used to develop a <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> model, which was then used to simulate an optimal fasting dose yielding an area under concentration (AUC) and maximum concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) of <jats:styled-content style=\"fixed-case\">NCMA<\/jats:styled-content> close to those obtained with the fed dose. <jats:styled-content style=\"fixed-case\">NCMA<\/jats:styled-content> concentrations were best characterized by a two\u2010compartment model with first\u2010order absorption linked to a recycling compartment to account for the multiple concentration peaks observed. Food increased bioavailability 2.2 times and decreased the absorption rate constant 0.58 times. Recycling event times were estimated to be 3.56, 7.99 and 24.0 hr. The optimal fast dose was 2.0 times higher than the fed dose, and the resulting difference in drug exposure between the fasting and fed dose was 7.5%. This work suggests that the <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> model developed can be applied to an optimal dosage regimen design for <jats:styled-content style=\"fixed-case\">NCMA<\/jats:styled-content> treatment.<\/jats:p>","DOI":"10.1111\/bcpt.12677","type":"journal-article","created":{"date-parts":[[2016,9,17]],"date-time":"2016-09-17T14:32:47Z","timestamp":1474122767000},"page":"270-277","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Quantitative Assessment of Food Effect on the Pharmacokinetics of Nano\u2010Crystallized Megestrol Acetate"],"prefix":"10.1111","volume":"120","author":[{"given":"Jinju","family":"Guk","sequence":"first","affiliation":[{"name":"Department of Pharmacology Yonsei University College of Medicine Seoul Korea"},{"name":"Brain Korea 21 plus Project for Medical Science Yonsei University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hankil","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Yonsei University College of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong Woo","family":"Chae","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Yonsei University College of Medicine Seoul Korea"},{"name":"Brain Korea 21 plus Project for Medical Science Yonsei University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyungsoo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Yonsei University College of Medicine Seoul 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