Cannabidiol lymphatic transport after oral administration assessed using a novel thoracic lymph duct cannulated...

Lymphatic transport of drugs after oral administration is an important physiological process in highly lipophilic compounds, such as cannabidiol (CBD). The majority of lymphatic transport studies have been historically conducted in anesthetized rats. However, this animal model differs significantly from the humans regarding both anatomical and physiological features. The aim of this study was therefore to develop a novel animal model using pigs and to provide an interspecies comparison for the lymphatic transport of CBD. The thoracic lymph duct was cannulated via thoracotomy in three pigs and lymph and blood were sampled from conscious animals to assess the lymphatic transport parameters and basic pharmacokinetic parameters of CBD administered in two distinct drug formulations (sesame oil-based solution and nanoemulsion) using a two-period cross-over study design. The mean ± SD oral bioavailability (F) was 6.1 ± 0.9% for the oil solution and 9.2 ± 6.6% for the nanoemulsion. The relative bioavailability via lymph (F_RL), i.e. the percentage of the systemically available drug that has been transported through the mesenteric lymph, was 20 ± 10% and 11 ± 13%, respectively. Whereas the F_RL for the oil solution was 2.3-fold lower in pigs compared to rats, the F_RL for the nanoemulsion was almost identical for both species. In conclusion, the lymphatic transport of CBD plays an important role after its oral administration. The particular parameters differed significantly between the rodent and higher non-rodent species. The use of higher species models is therefore warranted for the lymphatic transport assessment in settings close to humans.