{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:46:41Z","timestamp":1782949601231,"version":"3.54.5"},"reference-count":24,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"JSPS KAKENHI","award":["19K07023"],"award-info":[{"award-number":["19K07023"]}]},{"name":"JSPS KAKENHI","award":["23K04790"],"award-info":[{"award-number":["23K04790"]}]},{"name":"a Grant-in-Aid for Scientific Research from Ministry of Education, Science, Sports and Culture of Japan","award":["08877321"],"award-info":[{"award-number":["08877321"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Aerosol Medicine and Pulmonary Drug Delivery"],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction:<\/jats:title>\n                    <jats:p>\n                      Detailed understanding of the absorption mechanisms of compounds in the lungs is important for developing effective systems for the pulmonary administration of drugs. This study analyzed the pharmacokinetics of model compounds instilled into the mouse lungs using\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      electron spin resonance (ESR) spectroscopy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>An aqueous solution of a nitroxyl probe with cationic, anionic, or neutral groups was instilled into the lungs of healthy mice at high concentrations as model drugs, and the behavior of the probes was assessed using concentration-dependent changes in the linewidths of ESR signals obtained in live mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>When solutions of nitroxyl probes at high concentrations, which produce broad ESR signals, were instilled into the mouse lungs, sharp ESR signals originating from diluted probes were superimposed onto broad signals. Broad signals decreased at various rates for all probes depending on their lipophilicity. Sharp signals for neutral probe and anionic probe immediately increased after instillation and then decreased. Sharp signals for cationic probe with a quaternary ammonium group continued to increase after instillation. Pharmacokinetic analysis of the blood concentrations of these probes suggests that the probes are distributed to lung tissues in addition to the blood. The concentration dependence of the initial velocity of broad signal decay suggests the possibility that the transfer of charged probes from the alveolar space to the bloodstream may be mediated by transporters, whereas a neutral probe may be transferred via passive diffusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      The differences in pharmacokinetic behavior in lungs could be examined\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      among model compounds with different charge states.\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      ESR spectroscopy is a powerful tool for the\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      analysis of pulmonary pharmacokinetics, in combination with nitroxyl probes as model drugs.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/19412711251379678","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T16:07:18Z","timestamp":1759248438000},"page":"177-184","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic Analysis of Compounds Instilled into the Mouse Lung: Study with\n                    <i>In Vivo<\/i>\n                    Electron Spin Resonance Spectroscopy and Nitroxyl Spin Probes as Model Drugs"],"prefix":"10.1177","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2074-4472","authenticated-orcid":false,"given":"Jin-Yi","family":"Han","sequence":"first","affiliation":[{"name":"Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Keimyung University Dongsan Medical Center, Daegu, Republic of Korea."},{"name":"Faculty of Pharmaceutical Sciences. Kyushu University, Fukuoka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7071-0628","authenticated-orcid":false,"given":"Keizo","family":"Takeshita","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences. Kyushu University, Fukuoka, Japan."},{"name":"Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoko","family":"Okazaki","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6992-1658","authenticated-orcid":false,"given":"Hideo","family":"Utsumi","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences. Kyushu University, Fukuoka, Japan."},{"name":"School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.4155\/tde.13.67"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/rr58"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2005.02.010"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/tomography7030039"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.211433"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0891-5849(00)00501-3"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.06.008"},{"key":"e_1_3_2_9_2","first-page":"177","volume-title":"Applied Biopharmaceutics & Pharmacokinetics","author":"Duan JZ","year":"2016","unstructured":"Duan JZ. Pharmacokinetics of oral absorption. In: Applied Biopharmaceutics & Pharmacokinetics, Seventh Edition. (Shargel L, , Yu ABC. eds), McGraw-Hill: New York; 2016; pp. 177\u2013204."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.28499"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0891-5849(98)00278-0"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.3109\/10715769709097819"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291x(90)91597-l"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0891-5849(98)00314-1"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910100211"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4439(93)90161-s"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.066647"},{"key":"e_1_3_2_18_2","first-page":"378","volume-title":"Applied Biopharmaceutics & Pharmacokinetics","author":"Gerk PM","year":"2016","unstructured":"Gerk PM, , Yu ABC, , Shargel L. Physiologic factors related to drug absorption. In: Applied Biopharmaceutics & Pharmacokinetics, Seventh Edition. (Shargel L, , Yu ABC. eds.), McGraw-Hill: New York; 2016; pp. 378\u2013414."},{"issue":"1","key":"e_1_3_2_19_2","first-page":"17","article-title":"Whole mouse measurement of paramagnetism-loss of nitroxide free radical in lung with a L-band ESR spectrometer","volume":"29","author":"Takeshita K","year":"1993","unstructured":"Takeshita K, , Utsumi H, , Hamada A. Whole mouse measurement of paramagnetism-loss of nitroxide free radical in lung with a L-band ESR spectrometer. 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