Manuela Contin1,2, Susan Mohamed1, Margherita Santucci2,3, Monica Anna Maria Lodi4, Emilio Russo5, Oriano Mecarelli6. 1. IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. 2. Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. 3. IRCCS Istituto Delle Scienze Neurologiche di Bologna, Child Neuropsichiatry, Bologna, Italy. 4. Department of Neuroscience, Pediatric Neurology Unit and Epilepsy Center, "Fatebenefratelli e Oftalmico" Hospital, Milano, Italy. 5. Science of Health Department, School of Medicine, University Magna Graecia, Catanzaro, Italy. 6. Department of Human Neurosciences, Sapienza University, Rome, Italy.
Abstract
Background and Aim: Data on the clinical pharmacokinetics of cannabidiol (CBD) are scanty. We explored the effect of demographic and clinical variables on plasma concentrations of purified CBD in patients with Dravet (DS) and Lennox-Gastaut syndrome (LGS). Methods: The study design was an open, prospective, multicenter expanded access program (EAP). Venous blood samples were drawn from patients between 8 and 9 am, before the CBD morning dose, 12 h apart from the last evening dose, and then 2.5 h after their usual morning dose. Results: We collected 127 plasma samples (67-morning pre-dosing and 60 post-dosing) from 43 patients (24 females, 19 males), 27 with LGS and 16 with DS. Mean ± standard deviation age was 26 ± 15 years. Duration of CBD treatment averaged 4.2 ± 2.9 months at 13.2 ± 4.6 mg/kg/day. CBD median trough plasma concentration was 91 ng/ml; it doubled to 190 ng/ml 2.5 h post-dosing (p < 0.001). Cannabidiol trough plasma concentrations were linearly related to daily doses (r = 0.564, p < 0.001). Median trough CBD plasma concentration-to-weight-adjusted dose ratio (C/D) was 32% higher (p < 0.02) in plasma samples from subjects aged 18 and over than in those under 18. Sex and concomitant antiseizure medications (ASMs) were not associated with significant variations in CBD C/D, but caution is required due to the potential influence of confounders. Conclusion: These are the first data on CBD pharmacokinetics in children and adults with LGS or DS in a real-world setting. The most relevant finding was the higher CBD C/D in adults. In practice, reduced weight-normalized doses might be required with aging to achieve the same CBD plasma levels.
Background and Aim: Data on the clinical pharmacokinetics of cannabidiol (CBD) are scanty. We explored the effect of demographic and clinical variables on plasma concentrations of purified CBD in patients with Dravet (DS) and Lennox-Gastaut syndrome (LGS). Methods: The study design was an open, prospective, multicenter expanded access program (EAP). Venous blood samples were drawn from patients between 8 and 9 am, before the CBD morning dose, 12 h apart from the last evening dose, and then 2.5 h after their usual morning dose. Results: We collected 127 plasma samples (67-morning pre-dosing and 60 post-dosing) from 43 patients (24 females, 19 males), 27 with LGS and 16 with DS. Mean ± standard deviation age was 26 ± 15 years. Duration of CBD treatment averaged 4.2 ± 2.9 months at 13.2 ± 4.6 mg/kg/day. CBD median trough plasma concentration was 91 ng/ml; it doubled to 190 ng/ml 2.5 h post-dosing (p < 0.001). Cannabidiol trough plasma concentrations were linearly related to daily doses (r = 0.564, p < 0.001). Median trough CBD plasma concentration-to-weight-adjusted dose ratio (C/D) was 32% higher (p < 0.02) in plasma samples from subjects aged 18 and over than in those under 18. Sex and concomitant antiseizure medications (ASMs) were not associated with significant variations in CBD C/D, but caution is required due to the potential influence of confounders. Conclusion: These are the first data on CBD pharmacokinetics in children and adults with LGS or DS in a real-world setting. The most relevant finding was the higher CBD C/D in adults. In practice, reduced weight-normalized doses might be required with aging to achieve the same CBD plasma levels.
Authors: Gianluca Dini; Eleonora Tulli; Giovanni Battista Dell'Isola; Elisabetta Mencaroni; Giuseppe Di Cara; Pasquale Striano; Alberto Verrotti Journal: Front Pharmacol Date: 2022-05-20 Impact factor: 5.988
Authors: Emily K Colvin; Amanda L Hudson; Lyndsey L Anderson; Ramyashree Prasanna Kumar; Iain S McGregor; Viive M Howell; Jonathon C Arnold Journal: Cancers (Basel) Date: 2022-08-05 Impact factor: 6.575
Authors: Luigi Francesco Iannone; Gabriele Arena; Domenica Battaglia; Francesca Bisulli; Paolo Bonanni; Antonella Boni; Maria Paola Canevini; Gaetano Cantalupo; Elisabetta Cesaroni; Manuela Contin; Antonietta Coppola; Duccio Maria Cordelli; Giovanni Cricchiuti; Valentina De Giorgis; Maria Fulvia De Leva; Marta De Rinaldis; Giuseppe d'Orsi; Maurizio Elia; Carlo Andrea Galimberti; Alessandra Morano; Tiziana Granata; Renzo Guerrini; Monica A M Lodi; Angela La Neve; Francesca Marchese; Silvia Masnada; Roberto Michelucci; Margherita Nosadini; Nicola Pilolli; Dario Pruna; Francesca Ragona; Anna Rosati; Margherita Santucci; Alberto Spalice; Nicola Pietrafusa; Pasquale Striano; Elena Tartara; Laura Tassi; Amanda Papa; Claudio Zucca; Emilio Russo; Oriano Mecarelli Journal: Front Neurol Date: 2021-05-20 Impact factor: 4.003