{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:08:39Z","timestamp":1779192519708,"version":"3.51.4"},"reference-count":38,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2016,2,9]],"date-time":"2016-02-09T00:00:00Z","timestamp":1454976000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Aerosol Medicine and Pulmonary Drug Delivery"],"published-print":{"date-parts":[[2016,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Understanding the relationship between dose, lung exposure, and drug efficacy continues to be a challenging aspect of inhaled drug development. An experimental inhalation platform was developed using mometasone furoate to link rodent lung exposure to its\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      pharmacodynamic (PD) effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We assessed the effect of mometasone delivered directly to the lung in two different rodent PD models of lung inflammation. The data obtained were used to develop and evaluate a mathematical model to estimate drug dissolution, transport, distribution, and efficacy, following inhaled delivery in rodents and humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Mometasone directly delivered to the lung, in both LPS and\n                      <jats:italic toggle=\"yes\">Alternaria alternata<\/jats:italic>\n                      rat models, resulted in dose dependent inhibition of BALf cellular inflammation. The parameters for our mathematical model were calibrated to describe the observed lung and systemic exposure profiles of mometasone in humans and in animal models. We found that physicochemical properties, such as lung fluid solubility and lipophilicity, strongly influenced compound distribution and lung retention.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Presently, we report on a novel and sophisticated mathematical model leading to improvements in a current inhaled drug development practices by providing a quantitative understanding of the relationship between PD effects and drug concentration in lungs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jamp.2015.1253","type":"journal-article","created":{"date-parts":[[2016,2,9]],"date-time":"2016-02-09T11:50:18Z","timestamp":1455018618000},"page":"362-377","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["Preclinical Experimental and Mathematical Approaches for Assessing Effective Doses of Inhaled Drugs, Using Mometasone to Support Human Dose Predictions"],"prefix":"10.1177","volume":"29","author":[{"given":"Michael","family":"Caniga","sequence":"first","affiliation":[{"name":"Merck Research Laboratories"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Cabal","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khamir","family":"Mehta","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Ross","sequence":"additional","affiliation":[{"name":"Rochester Institute of Technology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malgorzata A.","family":"Gil","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janice D.","family":"Woodhouse","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Eckman","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John R.","family":"Naber","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marissa K.","family":"Callahan","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciano","family":"Goncalves","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan E.","family":"Hill","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robbie L.","family":"Mcleod","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fraser","family":"McIntosh","sequence":"additional","affiliation":[{"name":"Discovery Research Services Charles River Laboratories","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark C.","family":"Freke","sequence":"additional","affiliation":[{"name":"Discovery Research Services Charles River Laboratories","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra A.G.","family":"Visser","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil","family":"Johnson","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Salmon","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milenko","family":"Cicmil","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2016,2,9]]},"reference":[{"key":"e_1_3_3_2_2","volume-title":"Global Surveillance, Prevention and Control of Chronic Respiratory Diseases: A Comprehensive Approach","author":"Bousquet J","year":"2007","unstructured":"Bousquet J, , and Khaltaev N, eds: Global Surveillance, Prevention and Control of Chronic Respiratory Diseases: A Comprehensive Approach. 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