Ignacio Bressan

Objective: Identifying factors influencing cannabidiol (CBD) exposure can optimize treatment efficacy and safety. We aimed to describe the population pharmacokinetics of CBD in children with drug‐resistant developmental and epileptic encephalopathies (DEEs) and assess the influence of environmental, pharmacological, and clinical characteristics on CBD systemic exposure.Methods: Data from two pharmacokinetic studies of patients aged 2–18 years with DEEs were included (N = 48 patients). Serial blood samples were collected during maintenance treatment, before and after the morning dose, and up to 6 h after a dose of a purified CBD oil formulation, with or without a normocaloric breakfast. CBD plasma concentrations were also available following administration of a CBD‐enriched formulation. Samples were quantified using a validated liquid chromatography/tandem mass spectrometry assay. A CBD population pharmacokinetic model was developed using nonlinear mixed‐effects modeling. The effects of formulation, concomitant food intake, and demographic, clinical, and pharmacological factors on CBD pharmacokinetics were evaluated. Simulated maximum plasma concentration (C_max) and area under the concentration–time curve between 0 and 12 h (AUC_0‐12) were calculated.Results: A one‐compartment model with transit compartments and first‐order elimination best described CBD pharmacokinetics. Mean values for CBD apparent clearance (CL/F) and volume of distribution (V/F) were 143.5 L/h and 1892.4 L, respectively. Weight was allometrically scaled for V/F and CL/F, sex was associated with V/F, and both formulation and food condition were associated with F (relative bioavailability). CBD C_max increased by 41% and AUC_0‐12 by 45% when CBD was administered with food compared to fasting. Dose‐normalized AUC_0‐12 was approximately 50% lower with CBD‐enriched oil compared to purified CBD.Significance: In the present study, we described the effects of food and formulation on CBD exposure in children with DEEs. Increased CBD exposure with food intake and significant changes in drug exposure when switching between CBD formulations should be considered in patient management.

Introduction An increasing number of rural communities express perception of health damage from glyphosate and other agrochemicals. We measure the presence of glyphosate in the human body, in order to create, together with the local community, a systemic model that highlights modifiable causal socio-environmental conditions. Materials and methods Participatory Action Research. Measurement of environmental factors and self-reported oncological disease were obtained in a three-stage probabilistic sampling (blocks, houses, family) of people living in French city - 9 de Julio-Buenos Aires. Glyphosate in urine was analyzed by liquid chromatography coupled to tandem mass spectrometry. The exposure pathway was obtained by interviewing positive cases. A conceptual systemic model was designed. Results of the total 46 blocks of French, 23 were included with systematic sampling and from the 76 houses selected (50%) one person was included in the study. Oncological disease was reported in 21.8% of the households. 13% of the population (95% CI 6.5-23) presented quantifiable glyphosate in urine in June 2023. Occupational exposure was ruled out in all cases. The main self-reported sources were: unloading agrochemicals in the nearby warehouse, the grain storage complex, pesticide drift and self-propelled sprayers that pass by on the street, variables belonging to economic and cultural conditions. A network of actors emerged who, gathered on a website, propose actions to the mayor’s office. Discussion This study has high external validity for public health decision makers regarding the determinants. It is necessary to notify the Argentine Integrated Health System, both suspected exposure and possibly related health events, and to design how to refer human samples to highly complex laboratories to measure pesticides. Conclusion the presence of glyphosate in urine was due to environmental exposure; It expresses a path of passive, involuntary and chronic absorption of environmental pollutants and is due to French’s agricultural activity with dominance of market forces in the system, poorly antagonized by care forces.