Kinetic study of a 2-hydroxypropyl-β-cyclodextrin-based formulation of all-trans-retinoic acid in Sprague-Dawley rats after oral or intravenous administration

Abstract

all-trans-Retinoic acid (ATRA, vitamin A acid, or tretinoin) is a potent chemotherapeutic agent for the treatment of acute promyelocytic leukemia (APL). Its poor aqueous solubility not only affects its oral absorption but also prevents it from forming an aqueous parenteral formulation. Recently, we developed a water-soluble formulation of ATRA with 2-hydroxypropyl-β- cyclodextrin (HPβCD). In present study, this formulation was tested in Sprague-Dawley rats. Kinetic study of ATRA was carried out after oral or intravenous administration. Though there were no statistical differences in any of the estimated pharmacokinetic parameters between ATRA sodium salt and HPβCD-based ATRA after intravenous administration, inclusion of ATRA into HPβCD was found to greatly improve the oral absorption of ATRA. (C) 2000 Wiley-Liss Inc.