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Pharm Res. 2009 Jun;26(6):1486-95. doi: 10.1007/s11095-009-9860-z. Epub 2009 Mar 12.

Intestinal lymphatic transport enhances the post-prandial oral bioavailability of a novel cannabinoid receptor agonist via avoidance of first-pass metabolism.

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Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria 3052, Australia.



To examine the effect of food on the oral bioavailability of a highly lipophilic, cannabinoid receptor agonist (CRA13) and to explore the basis for the food effect in lymph-cannulated and non-cannulated dogs.


Oral bioavailability was assessed in fasted and fed human volunteers and in lymph-cannulated dogs. In fasted dogs, the extent of absorption and oral bioavailability was also examined following administration of radiolabelled CRA13.


Food had a substantial positive effect on the oral bioavailability of CRA13 in human volunteers (4.3-4.9 fold increase in AUC(0 - infinity)) and in dogs. The absolute bioavailability of parent drug was low in fasted dogs (8-20%), in spite of good absorption (72-75% of radiolabelled CRA13 recovered in the systemic circulation). In post-prandial lymph-cannulated dogs, bioavailability increased to 47.5% and the majority (43.7%) of the dose was absorbed via the intestinal lymphatic system.


The positive food effect for CRA13 does not appear to result from increased post-prandial absorption. Rather these data provide one of the first examples of a significant increase in bioavailability for a highly lipophilic drug, which is stimulated via almost complete post-prandial transport into the lymph, in turn resulting in a reduction in first-pass metabolism.

[Indexed for MEDLINE]

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