Biopharmaceutics of beta-cyclodextrin derivative-based formulations of acitretin in Sprague-Dawley rats
| Autor: | Sui Yung Chan, Paul C. Ho, Hai-Shu Lin, Xin Liu |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Drug
Male media_common.quotation_subject Chemistry Pharmaceutical Pharmaceutical Science Administration Oral Etretinate Pharmacology Acitretin Biopharmaceutics Rats Sprague-Dawley Glucuronides Keratolytic Agents Pharmacokinetics Suspensions medicine Animals Bile Enterohepatic circulation Active metabolite media_common Cyclodextrins Chemistry beta-Cyclodextrins Bioavailability Rats Pharmaceutical Solutions Area Under Curve Injections Intravenous medicine.drug |
| Zdroj: | Journal of pharmaceutical sciences. 93(4) |
| ISSN: | 0022-3549 |
| Popis: | 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-beta-cyclodextrin (HPBCD)/randomly substituted methyl-beta-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 (approximately 40%) was excreted in the bile as beta-glucuronide conjugate and only trace amounts were excreted as unconjugated acitretin (approximately 0.5%). This finding further confirmed the importance of conjugated metabolism and biliary excretion in the elimination of this drug. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text