TY - JOUR
T1 - Cannabidiol in Pharmacoresistant Epilepsy
T2 - Clinical Pharmacokinetic Data From an Expanded Access Program
AU - Contin, Manuela
AU - Mohamed, Susan
AU - Santucci, Margherita
AU - Lodi, Monica Anna Maria
AU - Russo, Emilio
AU - Mecarelli, Oriano
AU - Bisulli, Francesca
AU - Boni, Antonella
AU - Cantalupo, Gaetano
AU - Cesaroni, Elisabetta
AU - Coppola, Antonietta
AU - Di Bonaventura, Carlo
AU - Fetta, Anna
AU - La Neve, Angela
AU - Matricardi, Sara
AU - Michelucci, Roberto
AU - Papa, Amanda
AU - Pilolli, Nicola
AU - Pulitano, Patrizia
AU - Ragona, Francesca
AU - Russo, Paola
AU - Striano, Pasquale
AU - Volpi, Lilia
AU - Zucca, Claudio
AU - CBD LICE Italy Study Group
N1 - Publisher Copyright:
© Copyright © 2021 Contin, Mohamed, Santucci, Lodi, Russo, Mecarelli and CBD LICE Italy Study Group.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/3/3
Y1 - 2021/3/3
N2 - 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.
AB - 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.
KW - antiseizure medication
KW - cannabidiol
KW - Dravet syndrome
KW - epilepsy
KW - Lennox–Gastaut syndrome
KW - pharmacokinetics
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U2 - 10.3389/fphar.2021.637801
DO - 10.3389/fphar.2021.637801
M3 - Article
AN - SCOPUS:85103308416
VL - 12
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
SN - 1663-9812
M1 - 637801
ER -