Traditionally Boswellia serrata extract is used in the Indian Ayurvedic medicine for the treatment of inflammatory diseases. In 2002 the EMEA designated Boswellia an orphan drug status for the treatment of peritumoral oedema. Pharmacokinetic studies yielded low plasma concentrations of the active ingredients 11-keto-beta-boswellic acid (KBA) and 3-acetyl-11-keto-beta-boswellic acid (AKBA). In continuation of the tests investigating the factors limiting bioavailability of boswellic acids, the present study examined the permeability of KBA and AKBA in human Caco-2 cell lines. In addition, the interaction of KBA and AKBA with the organic anion transporter OATP1B3 and the multi drug resistant proteins P-glycoprotein and MRP2 was evaluated using partly fluorescent-based assays. The permeability studies revealed poor permeability of AKBA and moderate absorption of KBA with a P(app) value of 1.69 x 10(-6) cm/s. Most of KBA and AKBA were found to be retained by the Caco-2 monolayer. Neither KBA nor AKBA could be identified as substrates of P-glycoprotein. However, both KBA and AKBA modulated the activity of OATP1B3 and MRP2, indicating that therapeutic relevant interactions with other anionic drugs may be expected. The results of the present study provide the first explanation for the pharmacokinetic properties of KBA and AKBA.