British journal of clinical pharmacology · 2025
Population pharmacokinetic modelling revealed large variability in oromucosal absorption of Δ9-tetrahydrocannabinol in older patients with poor appetite.
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Storgaard Ida Klitzing, Nielsen Rikke Lundsgaard, Houlind Morten Baltzer, Bornæs Olivia, Christensen Louise Westberg Strejby, Andersen Aino Leegaard, Juul-Larsen Helle Gybel, Jørgensen Lillian Mørch, Breindahl Torben, Jawad Baker Nawfal, Altintas Izzet, Andersen Ove, Lund Trine Meldgaard
Аннотация
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 Δ9-tetrahydrocannabinol (THC) and its active metabolite 11-hydroxy-Δ9-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 two or three sprays (2.7 mg THC and 2.5 mg cannabidiol per spray), with a dosing interval of 4 h. Blood samples were collected for up to 8 h to obtain plasma concentration-time data for non-linear mixed-effects modelling. 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-1) and other pathways (162 L h-1). Absorption of THC was modelled 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.
METHODS: We administered two fixed doses of Sativex® oromucosal spray to 20 patients, each dose consisting of two or three sprays (2.7 mg THC and 2.5 mg cannabidiol per spray), with a dosing interval of 4 h. Blood samples were collected for up to 8 h to obtain plasma concentration-time data for non-linear mixed-effects modelling. 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-1) and other pathways (162 L h-1). Absorption of THC was modelled 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.