Multiple oral dosing of valacyclovir in horses and ponies.

The study investigates the effects of multiple oral doses of valacyclovir on horses and ponies, concentrating on observing the exceedance of plasma concentrations above the EC(50)-value of acyclovir against equine herpesvirus 1 and its presence in nasal mucus and cerebrospinal fluid.

Objectives of the Research

• The main objective of this study was to examine whether multiple doses of valacyclovir, when administered orally to horses and ponies, could result in plasma concentrations that are higher than the EC(50) of acyclovir against Equine Herpesvirus 1 (EHV1). EC(50) denotes the Effective Concentration where 50% of viral replication is inhibited.
• The researchers also aimed to determine the concentration of acyclovir in nasal mucus and cerebrospinal fluid (CSF) after the administration of valacyclovir.

Methodology

• Four horses and two ponies were given dosages of 40 mg/kg valacyclovir orally, three times daily, over a period of four consecutive days.
• Blood samples were obtained from the animals prior to each dosage and one hour post-dosage to monitor the change in plasma concentrations of valacyclovir and acyclovir.
• Nasal mucus samples and cerebrospinal fluid were also collected as part of the study.

Results of the Study

• This dosage and administration regimen led to plasma concentrations that were higher than the EC(50) value for EHV1 for nearly 80% (for an isolate highly susceptible to acyclovir) to 60% (for an isolate less susceptible) of the treatment period.
• Concentrations of acyclovir were measurable in nasal mucus and CSF samples. However, they were lower than the EC(50), with CSF measurements ranging from 0.36-1.17 microg/mL and nasal mucus measurements between 0.11-0.23 microg/mL.

Implications of the Study

• The study suggests that multiple oral dosages of valacyclovir could be beneficial therapeutically, as valacyclovir plasma concentrations were maintained above the EC(50) value of acyclovir against EHV1 for more than 50% of the treatment period.
• Moreover, the presence of acyclovir in nasal mucus samples and cerebrospinal fluid indicates that valacyclovir is metabolized into acyclovir, which is the active anti-viral compound, and can reach the sites of potential infection even though the concentrations were lower than the EC(50).