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Antimicrobial agents and chemotherapy2007; 51(12); 4308-4314; doi: 10.1128/AAC.00116-07

Pharmacokinetics of acyclovir after intravenous infusion of acyclovir and after oral administration of acyclovir and its prodrug valacyclovir in healthy adult horses.

Abstract: 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 mug/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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Publication Date: 2007-09-10 PubMed ID: 17846132PubMed Central: PMC2167972DOI: 10.1128/AAC.00116-07Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study explores how the body absorbs and processes the drug acyclovir, administered orally and intravenously, and its prodrug valacyclovir in horses. The findings could be instrumental in designing an optimal dosage schedule for treating horses infected with equine herpesvirus.

Purpose and Design of Study

  • This research aimed to understand how well acyclovir, an antiviral medication, is absorbed and processed (pharmacokinetics) when given orally and intravenously to horses. This was also compared to the administration of its prodrug valacyclovir, which is a medicine that converts into acyclovir once inside the body.
  • Additionally, the researchers sought to use this pharmacokinetic data in conjunction with pharmacodynamic information, which is how the drug influences the body, to construct an effective dosage plan. The pharmacodynamic information used in this case were the 50% effective concentrations (EC50 values) from laboratory studies.

Methodology

  • The experiment was conducted on healthy adult horses with three different treatments: intravenous acyclovir, oral acyclovir, and oral valacyclovir. All three were given considering the horse’s body weight.
  • The study used high-performance liquid chromatography and fluorescence detection to measure the amount of the drug in plasma. Moreover, liquid chromatography-tandem mass spectrometry was used to determine the unbound plasma concentrations of the drug.

Key Findings

  • The study found that the peak concentration of acyclovir given intravenously was roughly the same for both the total and the unbound plasma concentrations. The average elimination half-life (time taken for the concentration of the drug to reduce by half in the body) ranged between 5.05 hours (total concentration) and 11.9 hours (unbound concentration).
  • The oral administration of acyclovir resulted in a low peak concentration in plasma (Cmax) and poor bioavailability (the portion of the drug that enters circulation when introduced into the body).
  • Conversely, valacyclovir administrated orally resulted in a ten times higher plasma peak concentration and an eight times better bioavailability than oral administration of acyclovir.
  • The study shows that intravenous acyclovir (at 10 mg/kg) and oral valacyclovir (at 20 mg/kg) reach concentrations within the sensitivity range of equine herpesvirus type 1 (EHV-1), a leading cause of viral disease in horses.

Implication and Future Directions

  • The study concludes that due to its higher bioavailability, valacyclovir is a better candidate for prevention and treatment in horses afflicted with EHV-1 compared to acyclovir.
  • The paper proposes that a dosage of 40 mg/kg valacyclovir, administered three times daily, should be enough to achieve plasma concentrations above the EC50 values.
  • This research could help in creating a better treatment regimen for horse-owners and veterinary hospitals, improving the health and wellbeing of the animals suffering from EHV-1.

Cite This Article

APA
Garré B, Shebany K, Gryspeerdt A, Baert K, van der Meulen K, Nauwynck H, Deprez P, De Backer P, Croubels S. (2007). Pharmacokinetics of acyclovir after intravenous infusion of acyclovir and after oral administration of acyclovir and its prodrug valacyclovir in healthy adult horses. Antimicrob Agents Chemother, 51(12), 4308-4314. https://doi.org/10.1128/AAC.00116-07

Publication

Antimicrobial agents and chemotherapy
ISSN: 0066-4804
NlmUniqueID: 0315061
Country: United States
Language: English
Volume: 51
Issue: 12
Pages: 4308-4314

Researcher Affiliations

Garré, B
  • Department of Pharmacology, Toxicology, Biochemistry, and Organ Physiology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
Shebany, K
    Gryspeerdt, A
      Baert, K
        van der Meulen, K
          Nauwynck, H
            Deprez, P
              De Backer, P
                Croubels, S

                  MeSH Terms

                  • Acyclovir / administration & dosage
                  • Acyclovir / analogs & derivatives
                  • Acyclovir / blood
                  • Acyclovir / pharmacokinetics
                  • Administration, Oral
                  • Algorithms
                  • Animals
                  • Antiviral Agents / administration & dosage
                  • Antiviral Agents / pharmacokinetics
                  • Chromatography, High Pressure Liquid / methods
                  • Horses
                  • Infusions, Intravenous
                  • Metabolic Clearance Rate
                  • Prodrugs / administration & dosage
                  • Prodrugs / pharmacokinetics
                  • Tandem Mass Spectrometry
                  • Valacyclovir
                  • Valine / administration & dosage
                  • Valine / analogs & derivatives
                  • Valine / pharmacokinetics

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