{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:10:56Z","timestamp":1788930656254,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006197","name":"Fonden til L\u00e6gevidenskabens Fremme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006197","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      Cannabis\u2010based medicines are gaining interest and being explored for new therapeutic indications, many of which commonly affect older medical patients. As most previous studies of the population pharmacokinetics of cannabinoids have been performed in healthy adults, this study aimed to investigate the population pharmacokinetics of \u0394\n                      <jats:sup>9<\/jats:sup>\n                      \u2010tetrahydrocannabinol (THC) and its active metabolite 11\u2010hydroxy\u2010\u0394\n                      <jats:sup>9<\/jats:sup>\n                      \u2010tetrahydrocannabinol (THC\u2010OH) in older medical patients with poor appetite.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We administered two fixed doses of Sativex\u00ae oromucosal spray to 20 patients, each dose consisting of two or three sprays (2.7\u00a0mg THC and 2.5\u00a0mg cannabidiol per spray), with a dosing interval of 4\u00a0h. Blood samples were collected for up to 8\u00a0h to obtain plasma concentration\u2010time data for non\u2010linear mixed\u2010effects modelling. Population pharmacokinetic models were developed for THC and THC\u2010OH sequentially, resulting in a combined parent\u2010metabolite model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found a one\u2010compartment model and a two\u2010compartment model to be the best fits for THC and THC\u2010OH, respectively, with apparent clearance of THC through conversion to THC\u2010OH (765\u2009L\u2009h\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) and other pathways (162\u2009L\u2009h\n                      <jats:sup>\u22121<\/jats:sup>\n                      ). Absorption of THC was modelled with a delay through three transit compartments. The inter\u2010 and intra\u2010individual variability on pharmacokinetic parameters was generally large (CV%\u2009=\u200940.2\u2010152%). Using the parent\u2010metabolite model, it was investigated whether physiological characteristics such as kidney function and body composition influence THC pharmacokinetics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The parent\u2010metabolite model describes and quantifies the pharmacokinetics of oromucosally administered THC in older medical patients with poor appetite. The covariate analysis did not show any clinically significant effect on pharmacokinetic parameters of THC or THC\u2010OH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70284","type":"journal-article","created":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T05:00:01Z","timestamp":1758344401000},"page":"504-514","source":"Crossref","is-referenced-by-count":5,"title":["Population pharmacokinetic modelling revealed large variability in oromucosal absorption of \u0394\n                    <sup>9<\/sup>\n                    \u2010tetrahydrocannabinol in older patients with poor appetite"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8650-6595","authenticated-orcid":false,"given":"Ida Klitzing","family":"Storgaard","sequence":"first","affiliation":[{"name":"Department of Drug Design and Pharmacology University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke 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