Improved oral bioavailability of artemisinin through inclusion complexation with beta- and gamma-cyclodextrins

The bioavailability of beta- and gamma -cyclodextrin artemisinin complexes was evaluated in comparison with a normal commercially available preparatio n, Artemisinin 250 (R). Twelve healthy male volunteers participated in the study conducted according to a three-way crossover design. The bioavailabil ity was compared using the parameters, total area under the plasma level-ti me curve (AUC(0-proportional to)), peak plasma concentration (C-max), and t ime to reach peak plasma concentration (T-max). A statistically significant difference was observed between the values of the complexes and Artemisini n 250 (R) for the three parameters. However, no statistically significant d ifference was observed between the values of the beta- and gamma -cyclodext rin complexes. Moreover, the 90% confidence interval for the ratio of the A UC(0-proportional to) values of the beta -cyclodextrin complex over those o f Artemisinin 250 (R) was estimated to be between 1.51-2.04, while that of C-max was between 1.73-2.93. For the gamma -cyclodextrin complex, the respe ctive intervals were 1.30-1.76 and 1.43-2.43. These findings indicated that the beta- and gamma -cyclodextrin complexes had a much higher rate and ext ent of bioavailability compared to Artemisinin 250 (R). In addition, the ab sorption of artemisinin was observed to be poor and negligible when the pre parations started to arrive in the colon. This could be attributed to poor dissolution of artemisinin in the semi-solid faecal matter in the lower par t of the gastrointestinal tract. (C) 2001 Elsevier Science BN. All rights r eserved.