Pharmacokinetics and pharmacodynamics of cannabis-based medicine in a patient population included in a randomized, placebo-controlled, clinical trial.

Autor: Hansen JS; Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Boix F; Section for Drug Abuse Research, Department of Forensic Sciences, Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway., Hasselstrøm JB; Department of Forensic Medicine, Aarhus University, Aarhus, Denmark., Sørensen LK; Department of Forensic Medicine, Aarhus University, Aarhus, Denmark., Kjolby M; Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark.; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Gustavsen S; Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark., Hansen RM; Spinal Cord Injury Center of Western Denmark, Viborg, Denmark., Petersen T; Department of Neurology, Hospital of Southern Jutland and Research Unit in Neurology, Aabenraa, Denmark.; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark., Sellebjerg F; Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark., Kasch H; Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Rasmussen PV; Department of Neurology, Aarhus University Hospital, Aarhus, Denmark., Finnerup NB; Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.; Danish Pain Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Saedder EA; Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark.; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Svendsen KB; Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Jazyk: angličtina
Zdroj: Clinical and translational science [Clin Transl Sci] 2024 Jan; Vol. 17 (1), pp. e13685. Date of Electronic Publication: 2023 Dec 06.
DOI: 10.1111/cts.13685
Abstrakt: Information on the pharmacokinetics (PK) and pharmacodynamics (PD) of orally administered cannabis-based medicine (CBM) in capsule formulation in patient populations is sparse. In this exploratory study, we aimed to evaluate the PK and PD in a probable steady state of CBM in neuropathic pain and spasticity in a population of patients with multiple sclerosis (MS). Of 134 patients participating in a randomized, double-blinded, placebo-controlled, trial, 23 patients with MS (17 female) mean age 52 years (range 21-67) were enrolled in this substudy. They received oral capsules containing Δ 9 -tetrahydrocannabinol (THC, n = 4), cannabidiol (CBD, n = 6), a combination (THC&CBD, n = 4), or placebo (n = 9). Maximum doses were 22.5 mg (THC) and 45 mg (CBD) a day divided into three administrations. PD parameters were evaluated for pain and spasticity. Blood samples were analyzed using an ultra-high-performance liquid chromatography-tandem mass spectrometer after protein precipitation and phospholipid removal. PK parameters were estimated using computerized modeling. The variation in daily dose and PK between individuals was considerable in a steady state, yet comparable with previous reports from healthy controls. Based on a simulation of the best model, the estimated PK parameters (mean) for THC (5 mg) were C max 1.21 ng/mL, T max 2.68 h, and half-life 2.75 h, and for CBD (10 mg) were C max 2.67 ng/mL, T max 0.10 h, and half-life 4.95 h, respectively. No effect was found on the PD parameters, but the placebo response was considerable. More immediate adverse events were registered in the active treatment groups compared with the placebo group.
(© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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