Stability of valacyclovir: Implications for its oral bioavailability

GLADYS E GRANERO AND GORDON L AMIDON

INTERNATIONAL JOURNAL OF PHARMACEUTICS

Elsevier

Año: 2005

0378-5173

font face="Times-Roman" size="1"> The absolute bioavailability of the prodrug valacyclovir, the l-valyl ester of acyclovir, after oral administration is ¡­54.5%. Since premature hydrolysis of this prodrug in the intestinal lumen may be a possible reason for its incomplete bioavailability and the chemical and enzymatic stability of the valacyclovir has been investigated. Release rates were investigated in both phosphate buffers with varying pH as well as in human and dog gastrointestinal fluids. The stability of the prodrug was found to be dependent on pH. This prodrug is chemically stable along the acidic pH side (under 4), while the prodrug degrades in alkaline medium through a base-catalyzed pseudo-first-order kinetics. The degradation of the prodrug valacyclovir progressed faster in intestinal fluid than in phosphat