Preliminary pharmacokinetic study of different preparations of acyclovir with beta-cyclodextrin.
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 beta-cyclodextrin. Acyclovir, its complex (1:1) with beta-cyclodextrin (acyclovir-beta-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 75 mg/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.
Luengo
Javiana
J
Department of Pharmacy, Faculty of Pharmacy, Casilla 237, Universidad de Concepción, Concepción, Chile.
Aránguiz
Teobaldo
T
Sepúlveda
Jacqueline
J
Hernández
Luis
L
Von Plessing
Carlos
C
D000212:Acyclovir / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D047392:beta-Cyclodextrins; C031215:betadex; D000212:Acyclovir