A Volumetric Absorptive Microsampling Technique to Monitor Cannabidiol Levels in Epilepsy Patients.

Sara Dubois,Sebastiano Barco,Emilio Russo,Gino Tripodi,Tommaso Lomonaco,Simona Lattanzi,Francesca Marchese,Federica Pigliasco,Pasquale Striano,Giuliana Cangemi

doi:10.3389/fphar.2020.582286

Abstract

Purpose: Interest in cannabis-based therapies has recently increased, due to the availability of cannabidiol (CBD) for the treatment of epilepsy without psychoactive effects. Therapeutic drug monitoring can prevent drug interactions and minimize drug toxicity. We evaluated a volumetric absorptive microsampling (VAMS) method combined with LC-MS/MS (liquid chromatography coupled to tandem mass spectrometry) for the quantification of CBD blood levels in patients with refractory epilepsy. Methods: Prospective observation of patients with Dravet syndrome receiving open-label, add-on GW-purified CBD (Epidyolex®) at different doses. CBD plasma samples were obtained from venipuncture and LC-MS/MS was used to measure CBD in venous and capillary blood samples collected by VAMS. Results: We enrolled five patients with a mean age of 13 (range: 4–27) years. CBD levels measured by VAMS on capillary blood did not differ from CBD levels measured in plasma by venipuncture (R 2 > 0.93). Conclusion: This proof-of-concept study suggests that VAMS allows monitoring of CBD plasma levels and can offer valuable support for personalized therapy in refractory epilepsy.

Highlights

Epilepsy is one of the most common brain chronic disorders, affecting around 70 million people of all ages worldwide (Hirtz et al, 2007; Zaccara and Schmidt, 2017)
We evaluated VAMS in combination with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for the quantification of CBD blood levels to be used in clinical practice to personalize the cannabis-based treatment of refractory epilepsy
We used a new microsampling method for the determination of CBD blood levels in patients with drug-resistant epilepsy using VAMS, which had previously proven useful for quantitative measurement of several venous and capillary blood drugs, including first and third-generation antiepileptic drugs (Velghe and Stove, 2018; DUrso et al, 2019), antibiotics (Barco et al, 2017) and immunosuppressants (Koster et al, 2019)

Summary

Introduction

Epilepsy is one of the most common brain chronic disorders, affecting around 70 million people of all ages worldwide (Hirtz et al, 2007; Zaccara and Schmidt, 2017). Despite the use of numerous therapeutic options, including third-generation antiseizure medications (ASMs), neuromodulation, surgical and VAMS Monitoring of Cannabidiol Treatment dietary interventions, 30% of patients continue to have seizures (Striano and Striano, 2009; Zaccara and Schmidt, 2017). The therapeutic potential of galenic preparations marketed to contain CBD/ THC was found to depend on preparation procedures, components concentration, and presence of other constituents (De Caro et al, 2017; Carcieri et al, 2018; Lattanzi et al, 2018; Lattanzi et al, 2019). Due to the heterogeneity of epilepsy clinical manifestations and interindividual response to old and new antiepileptic drugs, therapeutic drug monitoring (TDM) is a valuable clinical support in patients’ treatment

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