Biopharmaceutics of β-Cyclodextrin Derivative-Based Formulations of Acitretin in Sprague-Dawley Rats

Abstract

Acitretin, an active metabolite of etretinate, is as effective as etretinate in the treatment of psoriasis. Recently, we developed some water-soluble formulations of acitretin with 2-hydroxypropyl-β -cyclodextrin (HPBCD)/randomly substituted methyl-β-cyclodextrin (RMBCD). In this study, the biopharmaceutic properties of these formulations were tested in Sprague-Dawley rats. After single intravenous dosing (2.5, 5, or 10 mg/kg) with the HPBCD-based formulation, the area under the plasma concentration-time curve of acitretin increased proportionally with the dose and its clearance remained unchanged within the tested dose range. We also found that the RMBCD-based formulation of acitretin improved its bioavailability and decreased the variations in various pharmacokinetic parameters. The improved biopharmaceutic properties of RMBCD-based acitretin might be attributed to its enhanced aqueous solubility. The elimination of acitretin through bile excretion was also studied. Our results indicated that the major fraction of acitretin (∼-40%) was excreted in the bile as β-glucuronide conjugate and only trace amounts were excreted as unconjugated acitretin (∼0.5%). This finding further confirmed the importance of conjugated metabolism and biliary excretion in the elimination of this drug. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association.