Preliminary Pharmacokinetic Study of Different Preparations of Acyclovir with β-Cyclodextrin

• Published in: Journal of pharmaceutical sciences Vol. 91; no. 12; pp. 2593 - 2598
• Main Authors: Luengo, Javiana, Aránguiz, Teobaldo, Sepúlveda, Jacqueline, Hernández, Luis, Von Plessing, Carlos
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.12.2002; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association
• Subjects: acyclovir; Acyclovir - analysis; Acyclovir - blood; Acyclovir - pharmacokinetics; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Area Under Curve; beta-Cyclodextrins; Biological and medical sciences; Biological Availability; Chemistry, Pharmaceutical; Cyclodextrins - analysis; Cyclodextrins - blood; Cyclodextrins - pharmacokinetics; General pharmacology; Male; Medical sciences; microdialysis; Pharmaceutical technology. Pharmaceutical industry; pharmacokinetics; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; β-cyclodextrin; pharmacokinetics; acyclovir; microdialysis; β-cyclodextrin; Delivery system; Acyclic nucleoside; Purine nucleoside; Pharmaceutical technology; Rat; Oligosaccharide; Rodentia; Drug carrier; Bioavailability; Blood plasma; Vertebrata; Cyclodextrin; Mammalia; Microdialysis; Animal; Aciclovir; Dosage form; Antiviral; Inclusion compound; Pharmacokinetics
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.10245

Acyclovir has absorption problems, because of its low solubility and/or its saturable absorption mechanism, that take place in the small intestine in a passive, variable, and incomplete manner. The oral bioavailability of acyclovir is thereby affected and reaches only 15–30%. The purpose of this study was to investigate the possibility of increasing the oral availability of acyclovir by forming inclusion complexes of acyclovir with β-cyclodextrin. Acyclovir, its complex (1:1) with β-cyclodextrin (acyclovir–β-cyclodextrin complex), and a 50:50 mixture of acyclovir and the inclusion complex (acyclovir/complex mixture) as an aqueous suspension were administered intraintestinally to male Sprague-Dawley rats in doses equivalent to an acyclovir dose of 75mg/kg. Sequential samples of plasma were taken by microdialysis. The samples were analyzed by high-performance liquid chromatography with ultraviolet detection. Plasma concentration versus time curves show that the complex and the mixture of acyclovir/complex have a higher bioavailability and a pharmacokinetic profile than that of the drug itself. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association