Cannabinoid DMPK consultant: expert ADME and DDI support

Cannabinoids are among the most challenging small molecules to develop. They are highly lipophilic, extensively metabolised and prone to drug–drug interactions, and standard in vitro assays often give misleading results unless they are adapted for these compounds. I bring hands-on experience from the GW Pharmaceuticals team that took Epidiolex, the first FDA-approved cannabis-derived medicine, through NDA.

Why cannabinoid DMPK is different

• High lipophilicity: extensive non-specific binding to plastics, microsomes and hepatocytes can distort CLint, fu and IC50 values if not controlled for.
• Low and variable oral exposure: high first-pass metabolism and a pronounced food effect need to be understood early to support formulation and clinical design.
• Complex metabolism: multiple CYP and UGT pathways, and active or circulating metabolites (for example 7-OH-CBD and 11-OH-THC) that may need MIST assessment.
• DDI liability: cannabinoids can act as both perpetrators and victims of interactions, which regulators will expect you to characterise in line with ICH M12.

How I can help

• Early de-risking of novel cannabinoids and synthetic analogues: metabolic stability, pathways and DDI risk
• Designing in vitro assays that account for non-specific binding and solubility limits
• Regulatory in vitro DDI packages (CYP and UGT inhibition and induction, transporters) to ICH M12
• Metabolite identification and MIST strategy for major human metabolites
• Radiolabelled ADME, PK/TK and human dose prediction
• Authoring IND Modules 2.6.4/2.6.5, Investigator’s Brochure sections and responses to regulator questions
• Selecting and managing CROs with cannabinoid experience

Experience you can rely on

With more than 30 years in DMPK across pharma, biotech and CROs, I have contributed DMPK and DDI support to four successful NDAs, including Epidiolex as a member of the GW Pharmaceuticals NDA team, where I was ADME Leader. I work either embedded in your project team or as an independent adviser by the hour.