{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T21:51:53Z","timestamp":1772142713202,"version":"3.50.1"},"reference-count":10,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T00:00:00Z","timestamp":1595203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"REACTing"},{"name":"REsearch & ACtion emergING infectious diseases"},{"DOI":"10.13039\/501100001677","name":"INSERM","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The combination lopinavir\/ritonavir is recommended to treat HIV-infected patients at the dose regimen of 400\/100\u2005mg q12h, oral route. The usual lopinavir trough plasma concentrations are 3000\u20138000\u2005ng\/mL. A trend towards a 28\u2005day mortality reduction was observed in COVID-19-infected patients treated with lopinavir\/ritonavir.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To assess the plasma concentrations of lopinavir and ritonavir in patients with severe COVID-19 infection and receiving lopinavir\/ritonavir.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients and methods<\/jats:title>\n                  <jats:p>Mechanically ventilated patients with COVID-19 infection included in the French COVID-19 cohort and treated with lopinavir\/ritonavir were included. Lopinavir\/ritonavir combination was administered using the usual adult HIV dose regimen (400\/100\u2005mg q12h, oral solution through a nasogastric tube). A half-dose reduction to 400\/100\u2005mg q24h was proposed if lopinavir Ctrough was &amp;gt;8000\u2005ng\/mL, the upper limit considered as toxic and reported in HIV-infected patients. Lopinavir and ritonavir pharmacokinetic parameters were determined after an intensive pharmacokinetic analysis. Biological markers of inflammation and liver\/kidney function were monitored.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Plasma concentrations of lopinavir and ritonavir were first assessed in eight patients treated with lopinavir\/ritonavir. Median (IQR) lopinavir Ctrough reached 27\u202f908\u2005ng\/mL (15\u202f928\u201332\u202f627). After the dose reduction to 400\/100\u2005mg q24h, lopinavir\/ritonavir pharmacokinetic parameters were assessed in nine patients. Lopinavir Ctrough decreased to 22\u202f974\u2005ng\/mL (21\u202f394\u201332\u202f735).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In mechanically ventilated patients with severe COVID-19 infections, the oral administration of lopinavir\/ritonavir elicited plasma exposure of lopinavir more than 6-fold the upper usual expected range. However, it remains difficult to safely recommend its dose reduction without compromising the benefit of the antiviral strategy, and careful pharmacokinetic and toxicity monitoring are needed.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaa261","type":"journal-article","created":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T19:09:55Z","timestamp":1590692995000},"page":"2657-2660","source":"Crossref","is-referenced-by-count":13,"title":["Pharmacokinetics of lopinavir\/ritonavir oral solution to treat COVID-19 in mechanically ventilated ICU patients"],"prefix":"10.1093","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4670-8288","authenticated-orcid":false,"given":"Minh Patrick","family":"L\u00ea","sequence":"first","affiliation":[{"name":"AP-HP, Bichat Claude Bernard Hospital, Pharmacology-Toxicology Department, 75018 Paris, France"},{"name":"INSERM, UMRS-1144, Universit\u00e9 de Paris, 75006 Paris, 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Hingrat","sequence":"additional","affiliation":[{"name":"AP-HP, Bichat Claude Bernard Hospital, Virology Department, 75018 Paris, France"},{"name":"IAME, INSERM, UMRS1137, Universit\u00e9 de Paris, 75018 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Veyrier","sequence":"additional","affiliation":[{"name":"AP-HP, Bichat Claude Bernard Hospital, Pharmacy Department, 75018 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliette","family":"Kauv","sequence":"additional","affiliation":[{"name":"AP-HP, Bichat Claude Bernard Hospital, Pharmacology-Toxicology Department, 75018 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romain","family":"Sonneville","sequence":"additional","affiliation":[{"name":"AP-HP, Bichat Claude Bernard Hospital, Medical and Infectious Diseases ICU (MI2), 75018 Paris, France"},{"name":"IAME, INSERM, UMRS1137, Universit\u00e9 de Paris, 75018 Paris, 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