The aim of this work was to evaluate the impact of sulfobutyl ether I?-cyclodextrin ((SBE)7a??m-I?-CD; CaptisolA?) on the in vivo pharmacokinetics of melphalan in rats. Melphalan is a chemically unstable antineoplastic drug which in the current commercial formulation (AlkeranA? for Injection) has some limitations with regard to solubility, stability and biocompatibility. Melphalan formulations containing (SBE)7a??m-I?-CD have previously been evaluated in vitro and shown to significantly reduce the rate of degradation and to simplify the reconstitution procedure for lyophilised melphalan. In this study, melphalan was administered intravenously in rats in formulations that either contain (SBE)7a??m-I?-CD or a co-solvent system (i.e. the commercial formulation). Pharmacokinetic parameters, including half-life, volume of distribution, clearance and extent of renal elimination of melphalan were essentially unchanged between the two formulations. These findings indicate that the pharmacokinetics of melphalan are not altered in the presence of (SBE)7a??m-I?-CD consistent with a rapid shift in the equilibrium to the fully dissociated drug from the fraction associated with the cyclodextrin host molecule upon intravenous administration.