ArticleEuropean journal of drug metabolism and pharmacokinetics2026
Potential Role of CYP3A4 in Determining In Vivo Exposure to Cannabidiol (CBD) and its Active Metabolite 7-OH-CBD: Evidence from an In Vitro Study.
Article in European journal of drug metabolism and pharmacokinetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPlasma concentration of cannabidiol (CBD) is a determining factor for its antiseizure efficacy. Since CBD bioavailability decreases with increasing dose, pharmacokinetic drug-drug interactions that reduce its metabolic clearance may represent an alternative strategy to increase systemic exposure without further dose escalation.
objectiveTo investigate in vitro how combinations of antiseizure medications (ASMs) with varying cytochrome P450 (CYP450) inhibitory properties influence the metabolism of CBD and 7-OH-CBD.
methodsCBD was incubated with human liver microsomes (HLMs) either alone or in the presence of combinations of two to four commonly prescribed ASMs. These ASMs included valproic acid, clobazam, stiripentol, topiramate, zonisamide, felbamate, perampanel, ethosuximide, rufinamide, lamotrigine, levetiracetam and gabapentin. CBD, 7-OH-CBD and 7-COOH-CBD concentrations were quantified at eight time points by high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Depletion kinetics, metabolite formation rates, and in vitro intrinsic clearance (CL
resultsKetoconazole markedly reduced the CL
conclusionASMs with CYP3A4-inhibitory potential may alter systemic exposure to both CBD and its active metabolite, 7-OH-CBD, as demonstrated in vitro. However, co-administration of CBD with CYP3A4-substrate ASMs or CYP2C19 inhibitors is predicted to result in only modest increases in CBD exposure.
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Registered trials
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