SP-303 small-particle aerosol treatment of influenza A virus infection in mice and respiratory syncytial virus infection in cotton rats.
A natural plant product, SP-303, was administered by small-particle aerosol to influenza A/HK virus-infected mice and RSV-infected cotton rats. Aqueous SP-303 at 2 mg/ml in the Collison nebulizer reservoir generated an aerosol with an output of 26 micrograms/l and a particle size distribution of 1.4 microns +/- 4.6 (MMAD +/- GSD). SP-303 at a dosage of 0.5-9.4 mg/kg per day administered for 3-4 days significantly increased both the rate and duration of survival of mice lethally infected with influenza A/HK virus. SP-303 was toxic to mice at 16 mg/kg per day as indicated by weight loss and a decrease in the duration of survival compared to control animals. From these data, a maximum therapeutic index (T.I.) of 12 was calculated. SP-303 given 3-4 days at dosages of 1.3-9.8 mg/kg per day was effective in reducing the pulmonary titer of RSV in infected cotton rats. However, at the 18.7 mg/kg per day dose a significant weight loss compared to control animals was observed; a T.I. of < or = 14 was estimated. These experiments demonstrate that aerosol administration of SP-303 was effective in the treatment of influenza A-infected mice and of RSV-infected cotton rats.
Gilbert
B E
BE
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX 77030.
Wyde
P R
PR
Wilson
S Z
SZ
Meyerson
L R
LR
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001704:Biopolymers; D002392:Catechin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009980:Influenza A virus; D007251:Influenza, Human / Q000188:drug therapy* / Q000382:microbiology; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D012136:Respiratory Syncytial Viruses; D010253:Respirovirus Infections / Q000188:drug therapy* / Q000382:microbiology; D013810:Therapeutic Equivalency; D044945:Proanthocyanidins
D000336:Aerosols; D000998:Antiviral Agents; D001704:Biopolymers; D002392:Catechin; D010936:Plant Extracts; C546704:crofelemer; D044945:Proanthocyanidins