6(A)-O-[2-(3-Benzoylphenyl)propinoyl]-alpha-cyclodextrin (KP-alpha-CyD conjugate), in which an anti-inflammatory drug, ketoprofen (KP), is covalently bound to one of the primary hydroxyl groups of alpha-cyclodextrin, was prepared, and its release behavior in vitro and in vivo was investigated. Further, the CyD conjugate-based repeated- and prolonged-release systems were designed by combining the conjugate (used as a delayed-release fraction) with the KP-2-hydroxypropyl-beta-CyD (HP-beta-CyD) complex (used as a fast-release fraction) or with KP-ethylcellulose (EC) solid dispersion (used as a slow-release fraction), respectively. The conjugate released KP only in rat cecum and colonic contents, whereas it was stable in other biological fluids of rats. The conjugate showed a typical delayed-release pattern after oral administration to rats, i.e., plasma levels of KP increased after a lag time of about 3 h and reached a maximum concentration at about 7 h. On the other hand, the non-covalent inclusion complex of KP with HP-beta-CyD gave a rapid increase in plasma drug levels, and the KP-EC solid dispersion retarded slightly the increase of plasma levels. The co-administration of the conjugate and the HP-beta-CyD complex gave a typical repeated release profile, i.e., double peaks were observed at about 1-2 and 8-12 h in plasma KP levels. On the other hand, the co-administration of the conjugate and the EC solid dispersion gave a typical sustained-release pattern of KP, i.e., a constant plasma KP level was maintained for at least 24 h. These repeated or long circulating release patterns in plasma KP levels after oral administration were clearly reflected in the anti-inflammatory effect using rats with carageenan-induced acute edema in paw. The results suggest that various release-controlled preparations can be designed by employing CyD conjugates in combination with other carriers with different releasing properties.