Population pharmacokinetics of Δ 9 -tetrahydrocannabinol and an active metabolite in older patients with poor appetite

Population pharmacokinetics of Δ 9 -tetrahydrocannabinol and an active metabolite in older patients with poor appetite | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL British Journal of Clinical Pharmacology This is a preprint and has not been peer reviewed. Data may be preliminary. 8 May 2025 V1 Latest version Share on Population pharmacokinetics of Δ 9 -tetrahydrocannabinol and an active metabolite in older patients with poor appetite Authors : Ida Storgaard 0000-0001-8650-6595 [email protected] , Rikke Nielsen , Morten Houlind 0000-0003-4058-3012 , Olivia Bornaes , Louise Christensen 0009-0006-8954-2675 , Aino Andersen , Helle Juul-Larsen , … Show All … , Lillian Jørgensen , Torben Breindahl , Baker Jawad , Izzet Altintas , Ove Andersen , and Trine Lund 0000-0001-8598-2880 Show Fewer Authors Info & Affiliations https://doi.org/10.22541/au.174669335.55509973/v1 342 views 270 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Aim: Cannabis-based 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 THC and its active metabolite 11-hydroxy-Δ 9 -tetrahydrocannabinol (THC-OH) in older medical patients with poor appetite. Methods: We administered two fixed doses of Sativex ® oromucosal spray to 20 patients, each dose consisting of 2 or 3 sprays (2.7 mg THC and 2.5 mg cannabidiol per spray), with a dosing interval of four hours. Blood samples were collected for up to eight hours to obtain plasma concentration-time data for non-linear mixed-effects modeling. Population pharmacokinetic models were developed for THC and THC-OH sequentially, resulting in a combined parent-metabolite model. Results: We found a one-compartment model and a two-compartment model to be the best fits for THC and THC-OH, respectively, with apparent clearance of THC through conversion to THC-OH (765 L/h) and other pathways (162 L/h). Absorption of THC was modeled with a delay through three transit compartments. The inter- and intra-individual variability on pharmacokinetic parameters was generally large (CV% = 40.2-152%). Using the parent-metabolite model, it was investigated whether physiological characteristics such as kidney function and body composition influence THC pharmacokinetics. Conclusion: the parent-metabolite 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-OH. Supplementary Material File (manuscript_poppk of thc.docx) Download 65.95 KB Information & Authors Information Version history V1 Version 1 08 May 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Collection British Journal of Clinical Pharmacology Keywords addiction medicine cannabinoids geriatrics pharmacodynamics pharmacokinetics pharmacometrics population analysis Authors Affiliations Ida Storgaard 0000-0001-8650-6595 [email protected] University of Copenhagen Faculty of Health and Medical Sciences View all articles by this author Rikke Nielsen Copenhagen University Hospital - Amager & Hvidovre View all articles by this author Morten Houlind 0000-0003-4058-3012 Copenhagen University Hospital View all articles by this author Olivia Bornaes Copenhagen University Hospital - Amager & Hvidovre View all articles by this author Louise Christensen 0009-0006-8954-2675 Hvidovre Hospital View all articles by this author Aino Andersen Copenhagen University Hospital - Amager & Hvidovre View all articles by this author Helle Juul-Larsen Hvidovre Hospital View all articles by this author Lillian Jørgensen Hvidovre Hospital View all articles by this author Torben Breindahl North Denmark Regional Hospital View all articles by this author Baker Jawad Hvidovre Hospital View all articles by this author Izzet Altintas Copenhagen University Hospital - Amager & Hvidovre View all articles by this author Ove Andersen Hvidovre Hospital View all articles by this author Trine Lund 0000-0001-8598-2880 University of Copenhagen View all articles by this author Metrics & Citations Metrics Article Usage 342 views 270 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Ida Storgaard, Rikke Nielsen, Morten Houlind, et al. Population pharmacokinetics of Δ 9 -tetrahydrocannabinol and an active metabolite in older patients with poor appetite. Authorea . 08 May 2025. DOI: https://doi.org/10.22541/au.174669335.55509973/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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