Cannabidiol in Pharmacoresistant Epilepsy: Clinical Pharmacokinetic Data From an Expanded Access Program
| Autor: | Contin M., Mohamed S., Santucci M., Lodi M. A. M., Russo E., Mecarelli O., Bisulli F., Boni A., Cantalupo G., Cesaroni E., Coppola A., Di Bonaventura C., Fetta A., La Neve A., Matricardi S., Michelucci R., Papa A., Pilolli N., Pulitano P., Ragona F., Russo P., Striano P., Volpi L., Zucca C. |
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| Přispěvatelé: | Contin, M., Mohamed, S., Santucci, M., Lodi, M. A. M., Russo, E., Mecarelli, O., Bisulli, F., Boni, A., Cantalupo, G., Cesaroni, E., Coppola, A., Di Bonaventura, C., Fetta, A., La Neve, A., Matricardi, S., Michelucci, R., Papa, A., Pilolli, N., Pulitano, P., Ragona, F., Russo, P., Striano, P., Volpi, L., Zucca, C. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Evening Gastroenterology 03 medical and health sciences cannabidiol 0302 clinical medicine Dravet syndrome Pharmacokinetics Internal medicine medicine Pharmacology (medical) antiseizure medication Pharmacology business.industry epilepsy Lennox–Gastaut syndrome pharmacokinetics lcsh:RM1-950 Venous blood Brief Research Report medicine.disease digestive system diseases 030104 developmental biology lcsh:Therapeutics. Pharmacology Concomitant Expanded access business Cannabidiol 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Frontiers in Pharmacology, Vol 12 (2021) Frontiers in Pharmacology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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