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The pharmacokinetics of drugs such as furosemide might be altered under hypoxic conditions, making it essential to establish different dose\u2010regimens to maintain therapeutic efficacy or to avoid toxic side effects at high altitude. Simultaneously, drug\u2013drug interactions (DDIs) mediated by OAT1 occur at high altitude, severely affecting furosemide pharmacokinetics. This study investigated the influence of acute exposure to high altitude at 4300\u00a0m on the renal excretion of furosemide in rats. Significant changes in physiological parameters and kidney histopathology were found after acute high altitude exposure. Compared with low altitude, the pharmacokinetics of furosemide and the expression level of OAT1 in kidney were significantly changed after rapid ascent to high altitude. Additionally, the down\u2010regulated OAT1 expression further sustained the potential mechanism for the decreased renal excretion of furosemide, resulting in extended residence of the drug in the human body. The elevation of AUC, C<jats:sub>max<\/jats:sub>, MRT, t<jats:sub>1\/2<\/jats:sub> of furosemide, and decreased CL at high altitude further reinforced the current findings. Moreover, the absorption of furosemide was markedly increased and renal excretion significantly declined after co\u2010administration of captopril, resulting in local drug interaction at high altitude. In conclusion, acute exposure to high altitude may significantly affect the renal excretion of furosemide and the pharmacokinetic parameters of furosemide were altered after co\u2010administration of captopril, which may then impact the conventional therapeutic dosage.<\/jats:p>","DOI":"10.1002\/bdd.2154","type":"journal-article","created":{"date-parts":[[2018,8,18]],"date-time":"2018-08-18T01:39:35Z","timestamp":1534556375000},"page":"378-387","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Evaluation of renal excretion and pharmacokinetics of furosemide in rats after acute exposure to high altitude at 4300 m"],"prefix":"10.1002","volume":"39","author":[{"given":"Bingfeng","family":"Luo","sequence":"first","affiliation":[{"name":"Key Laboratory of the Plateau Environmental Damage Control Lanzhou General Hospital of Lanzhou Military Command, PLA  Lanzhou China"},{"name":"College of Pharmacy Lanzhou University  Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Plateau Environmental Damage Control Lanzhou General Hospital of Lanzhou Military Command, PLA  Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Gansu Provincial Maternity and Child Care Hospital  Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbin","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Plateau Environmental Damage Control Lanzhou General Hospital of Lanzhou Military Command, PLA  Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juanhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Plateau Environmental Damage Control Lanzhou General Hospital of Lanzhou Military Command, PLA  Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Plateau Environmental Damage Control Lanzhou General Hospital of Lanzhou Military Command, PLA  Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anpeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Plateau Environmental Damage Control Lanzhou General Hospital of Lanzhou Military Command, PLA  Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9139-7311","authenticated-orcid":false,"given":"Rong","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Plateau Environmental Damage Control Lanzhou General Hospital of Lanzhou Military Command, PLA  Lanzhou China"},{"name":"College of Pharmacy Lanzhou University  Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,9,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.5414\/CPP43085"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.5414\/CPP42314"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmaid.2004.06.003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-14541-4_2"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00354.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11325-010-0368-x"},{"issue":"21","key":"e_1_2_8_8_1","first-page":"50","article-title":"Establishment of normal reference range of blood hematological and biochemical indicators of SPF wistar rats","volume":"6","author":"Fan J.","year":"2010","journal-title":"Journal of Public Health and Preventive Medicine"},{"issue":"9","key":"e_1_2_8_9_1","first-page":"1103","article-title":"Altitude illness: risk factors, prevention, presentation, and treatment","volume":"82","author":"Fiore D. 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