Pharmacokinetics of acyclovir in adult horses

Wilkins, Pamela A.; Papich, Mark G.; Sweeney, Raymond W.

doi:10.1111/j.1476-4431.2005.00145.x

Cited by 33 publications

(46 citation statements)

References 22 publications

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“…The peak concentrations after i.v. acyclovir administration were similar, i.e., 10.7 g/ml in this study versus 10.4 g/ml in the study of Wilkins et al (30). The mean AUC in this study (18.0 g ⅐ h/ ml) was also similar to the one reported by Wilkins et al (30) (19.2 g ⅐ h/ml), together with other PK parameters, such as total body clearance and the apparent volume of distribution at steady state.…”

Section: Vol 51 2007 Pharmacokinetics Of Acyclovir In Horses 4311supporting

confidence: 55%

“…However, as the t 1/2 of elimination was expressed as a harmonic mean in both studies and as large variations were noted among the various horses in our study, we can presume that these differences are not significant. Wilkins and colleagues (30) were unable to calculate the PK parameters after p.o. administration of acyclovir, as the plasma concentrations were below the lower limit of detection in all animals (LOQ, 156 ng/ml).…”

Section: Vol 51 2007 Pharmacokinetics Of Acyclovir In Horses 4311mentioning

confidence: 99%

“…administration of acyclovir, plasma samples were collected at 20, 40, and 60 min (the end of the infusion). Additional samples were obtained at 1.5, 2, 2.5, 3,4,5,6,8,10,16,23,30, and 48 h after the start of the infusion. For the p.o.…”

Section: Animalsmentioning

confidence: 99%

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Pharmacokinetics of Acyclovir after Intravenous Infusion of Acyclovir and after Oral Administration of Acyclovir and Its Prodrug Valacyclovir in Healthy Adult Horses

Garré¹,

Shebany²,

Gryspeerdt³

et al. 2007

Antimicrob Agents Chemother

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The purpose of this study was twofold. The first aim was to evaluate the oral bioavailability and pharmacokinetics (PKs) of acyclovir in horses after intravenous (i.v.) administration and after oral administration of acyclovir and its prodrug, valacyclovir. Second, we aimed to combine these PK data with pharmacodynamic (PD) information, i.e., 50% effective concentrations (EC 50 values) from in vitro studies, to design an optimal dosage schedule. Three treatments were administered to healthy adult horses: 10 mg of acyclovir/kg of body weight delivered as an i.v. infusion over 1 h, 20 mg of acyclovir/kg administered as tablets by nasogastric intubation, and 20 mg of valacyclovir/kg administered as tablets by nasogastric intubation. Total plasma concentrations were measured by a high-performance liquid chromatography method combined with fluorescence detection, while unbound plasma concentrations were determined by liquid chromatography-tandem mass spectrometry. The peak concentration of i.v. acyclovir was approximately 10 g/ml for both the total and the unbound plasma concentrations. The mean half-life of elimination was between 5.05 h (total concentration) and 11.9 h (unbound concentration). Oral administration of acyclovir resulted in low maximum concentration in plasma (C max ) and poor bioavailability. A 10-times-higher C max and an 8-times-higher bioavailability were achieved with oral administration of valacyclovir. The i.v. administration of 10 mg/kg acyclovir and the oral administration of 20 mg/kg valacyclovir achieved concentrations within the sensitivity range of equine herpesvirus type 1 (EHV-1). The higher bioavailability of valacyclovir makes it an attractive candidate for the prophylactic and/or therapeutic treatment of horses infected with EHV-1. The results from the PK/PD modeling showed that a dosage of 40 mg/kg valacyclovir, administered three times daily, would be sufficient to reach plasma concentrations above the EC 50 values.

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Section: Vol 51 2007 Pharmacokinetics Of Acyclovir In Horses 4311supporting

confidence: 55%

Section: Vol 51 2007 Pharmacokinetics Of Acyclovir In Horses 4311mentioning

confidence: 99%

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Pharmacokinetics of Acyclovir after Intravenous Infusion of Acyclovir and after Oral Administration of Acyclovir and Its Prodrug Valacyclovir in Healthy Adult Horses

Garré¹,

Shebany²,

Gryspeerdt³

et al. 2007

Antimicrob Agents Chemother

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“…As acyclovir is from patent since 1997 and generic alternatives are available, it seems attractive to use this drug for the treatment of horses during an outbreak. Previous studies (Wilkins et al, 2005) indicated that twice daily IV infusions of acyclovir (10 mg/kg) results in plasma concentrations above EC 50 -levels during the entire treatment interval. However, the EC 50 -value reported in their study was 0.3 mg/ml, which is 10-fold lower than the one we found.…”

Section: Discussionmentioning

confidence: 99%

In vitro susceptibility of six isolates of equine herpesvirus 1 to acyclovir, ganciclovir, cidofovir, adefovir, PMEDAP and foscarnet

Garré

Meulen

Nugent

et al. 2007

Veterinary Microbiology

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Equine herpesvirus 1 (EHV-1) is an important equine pathogen that causes respiratory disease, abortion, neonatal death and paralysis. Although vaccines are available, they are not fully protective and outbreaks of disease may occur in vaccinated herds. Therefore, there is an urgent need for effective antiviral treatment. For three abortigenic (94P247, 97P70 and 99P96) and three neuropathogenic isolates (97P82, 99P136 and 03P37), the effect of acyclovir, ganciclovir, cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) and foscarnet on plaque number was studied. Additionally, for isolate 97P70, the effect on plaque size was investigated. Ganciclovir was most potent in reducing plaque number, followed by PMEDAP and acyclovir. Adefovir and cidofovir were less effective and foscarnet was the least effective compound. There were no differences detected for acyclovir, ganciclovir, adefovir and PMEDAP between the abortigenic and neuropathogenic isolates. One abortigenic isolate (99P96) was more susceptible to cidofovir and two neuropathogenic isolates (99P136 and 03P37) were less susceptible to foscarnet. For isolate 97P70, all compounds resulted in a significant reduction of plaque size. The most remarkable effect was observed for cidofovir. It was 40-fold more effective in reducing plaque size than in reducing plaque number. In conclusion, ganciclovir was the most potent compound and therefore, may be a valuable candidate for the treatment of EHV-1 infections in horses. The antiviral effect of foscarnet on plaque number was highly dependent on the viral isolate tested. Therefore, it is no valuable antiviral for the treatment of herpesvirus-infections. Cidofovir, although less effective in reducing plaque number, had a strong effect on plaque size. #

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“…Treatment might have been not effective due to the reported poor bioavailability of 305 acyclovir (3-8%) (Wilkins et al, 2005, Bentz et al, 2006, Garré et al 2007 (Hart et al, 2008) and in some cases -as case 5 -an association between EMPF and 339 immunosuppression seems to be obvious.…”

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confidence: 99%