Multiple oral dosing of valacyclovir in horses and ponies

Abstract

The aim of the current study was to investigate whether multiple oral dosing of valacyclovir could result in plasma concentrations exceeding the EC(50)-value of acyclovir against equine herpesvirus 1 (EHV1) during the majority of the treatment period. Additionally, we wanted to determine the concentration of acyclovir in nasal mucus and cerebrospinal fluid (CSF). Valacyclovir was administered to four horses and two ponies, three times daily, at a dosage of 40 mg/kg, for four consecutive days. Blood was collected prior to each administration and 1 h after dosing. Nasal mucus samples and CSF were collected once during treatment; 1 h after the last administration. This dosage regimen resulted in plasma concentrations that were higher than the EC(50)-value of 1.7 microg/mL, i.e. EC(50) of an isolate highly susceptible to acyclovir, for 80% of the treatment period; and higher than the EC(50)-value of 3.0 microg/mL, i.e. EC(50) of an isolate less susceptible to acyclovir, for 60% of the treatment period. Concentration in nasal mucus samples and CSF was 0.36-1.17 microg/mL and 0.11-0.23 microg/mL, respectively. This study illustrates that multiple dosing of valacyclovir may result in a therapeutic benefit as plasma concentrations could be maintained above the EC(50)-value of acyclovir against EHV1 for more than 50% of the treatment period. Acyclovir could be detected in both nasal mucus samples and CSF. However, these concentrations were lower than the EC(50).

Use of antiviral medications against equine herpes virus associated disorders

“…2008, 2009). In one study, low concentrations of acyclovir could be detected in nasal mucus samples (mean 0.72 µg/ml; range 0.36–1.17 µg/ml) as well as cerebrospinal fluid samples (mean 0.16 µg/ml; range 0.11–0.23 µg/ml) (Garre et al. 2008).…”

“…2008). This suggests that there may not be an effective concentration of acyclovir in these tissues that would affect viral replication and shedding and is supported by one in vivo study (Garre et al. 2008).…”

“…As the respiratory and central nervous systems are target areas for different types of EHV‐1 infections, investigation into the concentration of acyclovir in these tissues has been measured after multiple dose administration of valacyclovir (40 mg/kg bwt, per os , q. 8 h) (Garre et al. 2008, 2009).…”

Pharmacokinetics of a single oral dose of acyclovir and valacyclovir in North American box turtles (Terrapenesp.)

“…Valacyclovir, an esterified version of acyclovir, is rapidly converted to acyclovir after absorption and has greater oral bioavailability than acyclovir (Garre et al. , 2008).…”

Occurrence of equine coital exanthema (ECE) in stallions in Japan and effectiveness of treatment with valacyclovir for ECE

“…In a previous study, a stallion and some mares with ECE responded well to application of acyclovir, and an inhibitory effect of acyclovir on EHV-3 was shown by plaque reduction assays [6]. Some researchers have used valacyclovir, a prodrug of acyclovir, for treatment of EHV-1 infection, but not for treatment of EHV-3 infection [8,9,10, 15]. Some studies showed that valacyclovir maintained an effective serum concentration for a longer time than did acyclovir [9, 10, 15].…”