{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T23:55:14Z","timestamp":1785455714641,"version":"3.56.0"},"reference-count":68,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T00:00:00Z","timestamp":1730160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T00:00:00Z","timestamp":1730160000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002830","name":"Centre National d\u2019Etudes Spatiales","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002830","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Therapeutic drug monitoring for astronauts faces limitations in conventional blood sampling and sample management onboard the international space station. Here, we explore the feasibility of dried blood spot (DBS) collection during parabolic flights (PF) to overcome these constraints.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We assessed the feasibility of blood deposition on blotting paper for preanalytical aspects in a PF using synthetic blood. Subsequently, DBS sampling validation was carried out in another PF campaign. Twenty volunteers participated in a pharmacokinetic study on caffeine and its metabolite, paraxanthine, conducted during parabolic flights. After &gt;18\u2009h caffeine washout, coffee (115\u2009mg), tea (30\u2009mg) or dark chocolate (11\u2009mg) were ingested by the participants. DBS samples were collected at baseline, during weightlessness and post\u2010flight. Caffeine and paraxanthine were analysed using liquid chromatography\u2013tandem mass spectrometry (LC\u2010MS\/MS). Genotyping for cytochrome P450\u20101A2 (CYP1A2) was performed and a metabolic ratio by area under the curve for caffeine and paraxanthine (AUC\n                      <jats:sub>PAX<\/jats:sub>\n                      \/AUC\n                      <jats:sub>CAF<\/jats:sub>\n                      ) for CYP1A2 was determined. A user experience survey was also conducted.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Full in\u2010flight pharmacokinetic study was feasible in seventeen volunteers with three unable to perform the sampling due to motion sickness. Nineteen participants (twelve males and seven females) completed pharmacokinetic profiles, with repeated pharmacokinetic studies for six participants. CYP1A2 genotyping resulted in eight ultrarapid, eleven intermediate, and one poor metabolizer. Among the women, four were on oestrogen contraceptives, a known inhibitor of CYP1A2, and were considered as poor metabolizers. Expected differences in kinetic profiles, consistent with consumption habits, the ingested dose and the genotypic\/phenotypic information, were observed. The mean caffeine AUC for coffee, tea and chocolate were 9419\u00a0\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ng.h.mL\">ng.h.mL<\/jats:ext-link>\n                      <jats:sup>\u22121<\/jats:sup>\n                      (95% confidence interval [CI]: 6222\u201312\u2009616,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910), 6917\u00a0\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ng.h.mL\">ng.h.mL<\/jats:ext-link>\n                      <jats:sup>\u22121<\/jats:sup>\n                      (95% CI: 2729\u201311\u2009105),\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097) and 3039\u00a0\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ng.h.mL\">ng.h.mL<\/jats:ext-link>\n                      <jats:sup>\u22121<\/jats:sup>\n                      (95% CI: 1614\u20134142,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200912), respectively. The mean paraxanthine AUC were 10\u2009566\u00a0\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ng.h.mL\">ng.h.mL<\/jats:ext-link>\n                      <jats:sup>\u22121<\/jats:sup>\n                      (95% CI: 6242\u201314\u2009890,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910), 4011\u00a0\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ng.h.mL\">ng.h.mL<\/jats:ext-link>\n                      <jats:sup>\u22121<\/jats:sup>\n                      (95% CI: 2305\u20135716,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097) and 3638\u00a0\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ng.h.mL\">ng.h.mL<\/jats:ext-link>\n                      <jats:sup>\u22121<\/jats:sup>\n                      (95% CI: 1589\u201340\u2009859,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200912), respectively. The mean metabolic ratio in oestrogen\u2010treated women was 0.53 (95% CI: 0.35\u20130.71) compared to 1.19 (95% CI: 0.99\u20131.33) in others. The mean metabolic ratio was 1.02 (95% CI: 0.81\u20131.23,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200915) on the ground and 1.10 (95% CI: 0.70\u20131.41,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200913) during the parabolic flights, with no significant difference observed between the two conditions. Overall participants were satisfied with the usability of the method.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DBS collection was safe, stable, feasible and well accepted in weightlessness. This method would offer valuable insights into human metabolism adaptation during long\u2010term spaceflight, addressing space pharmacology challenges.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.16320","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T04:47:50Z","timestamp":1730263670000},"page":"35-47","source":"Crossref","is-referenced-by-count":7,"title":["Feasibility of dried blood spot collection for caffeine pharmacokinetic studies in microgravity: Insights from parabolic flight campaigns"],"prefix":"10.1111","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7133-1400","authenticated-orcid":false,"given":"Audrey","family":"Derobertmasure","sequence":"first","affiliation":[{"name":"INSERM PARCC UMRS 970 Universit\u00e9 Paris\u2010Cit\u00e9  Paris France"},{"name":"Assistance Publique Des H\u00f4pitaux De Paris H\u00f4pital Europ\u00e9en Georges Pompidou, Clinical Pharmacology Unit and DMU CARTE  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Shean","family":"Toh","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Science University of Nottingham, University Park  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Verstuyft","sequence":"additional","affiliation":[{"name":"Molecular Genetics, Pharmacogenetics, and Hormonology Unit of Bic\u00eatre Paris\u2010Saclay University Hospitals, Assistance Publique\u2010H\u00f4pitaux de Paris, Bic\u00eatre Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srboljub","family":"Lukic","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and DMU BIOPHYGEN, Georges Pompidou European Hospital and Necker\u2010enfants malades Hospital, AP\u2010HP; Universit\u00e9 Paris\u2010Cit\u00e9, INEM U1151  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"De Sousa Carvalho","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and DMU BIOPHYGEN, Georges Pompidou European Hospital and Necker\u2010enfants malades Hospital, AP\u2010HP; Universit\u00e9 Paris\u2010Cit\u00e9, INEM U1151  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rapha\u00ebl","family":"Couronn\u00e9","sequence":"additional","affiliation":[{"name":"INSERM PARCC UMRS 970 Universit\u00e9 Paris\u2010Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Beauvalet","sequence":"additional","affiliation":[{"name":"INSERM PARCC UMRS 970 Universit\u00e9 Paris\u2010Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Chhun","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and DMU BIOPHYGEN, Georges Pompidou European Hospital and Necker\u2010enfants malades Hospital, AP\u2010HP; Universit\u00e9 Paris\u2010Cit\u00e9, INEM U1151  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Boutouyrie","sequence":"additional","affiliation":[{"name":"INSERM PARCC UMRS 970 Universit\u00e9 Paris\u2010Cit\u00e9  Paris France"},{"name":"Assistance Publique Des H\u00f4pitaux De Paris H\u00f4pital Europ\u00e9en Georges Pompidou, Clinical Pharmacology Unit and DMU CARTE  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270003257229"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270006291032"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552\u20104604.1995.tb04110.x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1980.213"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270005276620"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600560739"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010019\u20102679\u20103"},{"key":"e_1_2_11_9_1","volume-title":"Results of Life Sciences DSOs Conducted Aboard the Space Shuttle","author":"Cintron NM","year":"1987"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.1991.tb27292.x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11094\u2010009\u20100255\u20106"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1515\/dmdi\u20102021\u20100159"},{"key":"e_1_2_11_13_1","volume-title":"Results of Life Sciences DSOs Conducted Aboard the Space Shuttle","author":"Cintron NM","year":"1987"},{"key":"e_1_2_11_14_1","volume-title":"Bioavailability of promethazine during spaceflight","author":"Boyd JL","year":"2009"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1905875"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010022\u201003417\u20109"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000884"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11071962"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2020.461731"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.117.014407"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000643"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/npjmgrav.2016.25"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.15011"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41526\u2010023\u201000260\u20109"},{"key":"e_1_2_11_25_1","volume-title":"European SciSpace Roadmap","author":"Boutouyrie P","year":"2021"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12217\u2010009\u20109132\u2010x"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002\u20109610(05)80368\u2010X"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010014\u20100150\u20105"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsir.2024.100358"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.14.149"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2014.83"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010013\u20100115\u20100"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264\u2010020\u201000983\u20108"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2022.463724"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2017.07.029"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio\u20102018\u20100312"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2018.10.010"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15030979"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau8650"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00085"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.101909"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.12.007"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00000260"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14862"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2146"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107627"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00802.2015"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12743"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1080\/03602532.2017.1293683"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.065979"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.2011.01270.x"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2006.12.021"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/npjmgrav.2016.31"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12535"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781119615583.ch5"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2021\u20100533\u2010OA"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2019.104621"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2022.123539"},{"key":"e_1_2_11_59_1","unstructured":"NASA.3.001 Medical kit: contents and reference.2015.https:\/\/www.nasa.gov\/wp-content\/uploads\/2015\/03\/medical_kit_checklist_-_full_release.pdf. Accessed October 11 2024."},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0140764"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100043\u2010116492"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000936"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134\u2010020\u201006050\u20101"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000952"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113852"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11050701"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318\u2010023\u201000846\u20104"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00707\u201013"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9101379"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.16320","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcp.16320","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.16320","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T05:35:38Z","timestamp":1769146538000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.16320"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,29]]},"references-count":68,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/bcp.16320"],"URL":"https:\/\/doi.org\/10.1111\/bcp.16320","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,29]]}}}