Efficacy of a single intravenous dose of the neuraminidase inhibitor peramivir in the treatment of equine influenza.
Equine influenza A virus (EIV) of the H3N8 subtype is an important pathogen causing acute respiratory disease in horses. Peramivir is a selective inhibitor of the influenza virus neuraminidase (NA). The characteristics of peramivir are not only its capacity for parenteral administration, but also its strong affinity for NA and slow off-rate from the NA-peramivir complex, suggesting that it could lead to a prolonged inhibitory effect and thus allow a lower dosing frequency. The aims of this study were to evaluate the inhibitory efficacy of peramivir against the NA activities of EIV in vitro and the treatment efficacy of a single intravenous dose of peramivir in horses experimentally infected with EIV. Peramivir inhibited the activities of NA from the seven contemporary EIV strains in vitro, with 50% inhibitory concentrations ranging from 0.10 to 0.20 nmol/L. Horses treated with a single IV dose of peramivir (3,000 mg/600 mL/animal, 7.8-9.3mg/kg of bodyweight) showed significantly milder clinical signs (pyrexia, nasal discharge and cough) with a shorter duration than control horses injected with normal saline. Moreover, the mean duration of virus shedding for the horses treated with peramivir was significantly shorter than for the control horses. These findings suggested that a single IV administration of peramivir had good potential for the treatment of equine influenza, and may help to limit the spread of the disease in the horse population.
Epizootic Research Centre, Equine Research Institute, The Japan Racing Association, 1400-4 Shiba, Shimotsuke, Tochigi 329-0412, Japan. yamanaka@epizoo.equinst.go.jp
Takashi
T
Yamanaka
Hiroshi
H
Bannai
Manabu
M
Nemoto
Koji
K
Tsujimura
Takashi
T
Kondo
Masanori
M
Muranaka
Seiji
S
Hobo
Yo-Hei
YH
Minamijima
Masayuki
M
Yamada
Tomio
T
Matsumura
D000146:Acids, Carbocyclic; D000818:Animals; D000998:Antiviral Agents / Q000097:blood / Q000627:therapeutic use*; D002853:Chromatography, Liquid / Q000662:veterinary; D003517:Cyclopentanes / Q000097:blood / Q000627:therapeutic use*; D006146:Guanidines / Q000097:blood / Q000627:therapeutic use*; D006734:Horse Diseases / Q000188:drug therapy* / Q000821:virology; D006736:Horses; D053123:Influenza A Virus, H3N8 Subtype / Q000187:drug effects*; D007275:Injections, Intravenous / Q000662:veterinary; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000662:veterinary* / Q000821:virology; D053719:Tandem Mass Spectrometry / Q000662:veterinary
D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D006146:Guanidines; D009439:Neuraminidase; C414210:peramivir