{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T15:37:08Z","timestamp":1787931428983,"version":"build-2784847793"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T00:00:00Z","timestamp":1522627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Alpha\u20102 agonists are direct peripheral vasoconstrictors, which achieve these effects by activating vascular smooth muscle alpha\u20102 adrenoceptors. The impact of this response during dexmedetomidine infusion remains poorly quantified. Our goal was to investigate the pharmacokinetic (PK) and pharmacodynamic (PD, vasoconstriction) effects of a computer\u2010controlled dexmedetomidine infusion in healthy volunteers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      After local ethics committee approval, we studied 10 healthy volunteers. To study the peripheral vasoconstrictive effect of dexmedetomidine without concurrent sympatholytic effects, sympathetic fibres were blocked with a brachial plexus block. Volunteers received a dexmedetomidine target\u2010controlled infusion for 15\u00a0min, to a target concentration of 0.3\u00a0ng ml\n                      <jats:sup>\u20131<\/jats:sup>\n                      . Arterial blood samples were collected during and for 60\u00a0min after dexmedetomidine infusion for PK analysis. Peripheral vasoconstriction (PD) was assessed using finger photoelectric plethysmography. PK\/PD analysis was carried out using nonlinear mixed\u2010effect models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that the computer\u2010controlled infusion pump delivered mean concentrations greater than 0.3\u00a0ng ml\n                      <jats:sup>\u20131<\/jats:sup>\n                      over the 15\u2010min infusion duration. The peripheral vasoconstrictive effect correlated with dexmedetomidine plasma concentrations during and after the infusion. A three\u2010compartment model provided a better fit to the data than a two\u2010compartment model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We found that dexmedetomidine\u2010induced vasoconstriction is concentration dependent over time. Dexmedetomidine PK were best estimated by a three\u2010compartment model with allometric scaling. Our results may contribute to future modelling of dexmedetomidine\u2010induced haemodynamic effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.13571","type":"journal-article","created":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T12:13:25Z","timestamp":1519906405000},"page":"1364-1372","source":"Crossref","is-referenced-by-count":42,"title":["Pharmacokinetics and pharmacodynamics of dexmedetomidine\u2010induced vasoconstriction in healthy volunteers"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4839-2376","authenticated-orcid":false,"given":"Pekka","family":"Talke","sequence":"first","affiliation":[{"name":"University of California San Francisco  500 Parnassus Avenue, MUE455 San Francisco CA 94143 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2826-3019","authenticated-orcid":false,"given":"Brian J.","family":"Anderson","sequence":"additional","affiliation":[{"name":"University of Auckland  Private Bag 92024 Auckland 1001 New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00505799"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1139\/y95-068"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5276.803"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200307000-00014"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1213\/00000539-200108000-00006"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200503000-00010"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2010.03285.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13878"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:JOPA.0000012998.04442.1f"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:JOPA.0000012999.36063.4e"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199630050-00001"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.48.113006.094708"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1214\/ss\/1177013815"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-007-9081-1"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-017-0507-7"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000000740"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000539-200010000-00006"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aen316"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1989.103"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1987.tb03196.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.991"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-010-9157-1"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600840320"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200008000-00016"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcp.13571","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.13571","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T02:42:32Z","timestamp":1695004952000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.13571"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,2]]},"references-count":25,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1111\/bcp.13571"],"URL":"https:\/\/doi.org\/10.1111\/bcp.13571","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,2]]}}}